Epigenetics

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

119 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Cell-Penetrating Peptide-Bismuth Bicycles

43 | Feb 09 2024

The development of peptide-bismuth bicycles as cell-penetrating peptides showcases a groundbreaking leap in cellular uptake efficiency, offering a promising avenue for diverse biomedical applications. [Read the Full Post]

Reduction of excessive unfolded protein response by 4-phenylbutyric acid may mitigate procymidone-induced testicular damage in mice by changing the levels of circRNA Scar and circZc3h4

58 | Feb 08 2024

4-PBA demonstrates promising protective effects against PCM-induced testicular injury in mice, mitigating damage by regulating specific circRNAs, such as Scar and Zc3h4, and suppressing the unfolded protein response pathway. [Read the Full Post]

Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs

42 | Feb 04 2024

Frailty significantly amplifies the risk of serious infections and hospitalizations in rheumatoid arthritis patients starting biologic or targeted synthetic disease-modifying drugs, emphasizing the crucial need for tailored interventions in higher-risk populations. [Read the Full Post]

Binding of active Ras and its mutants to the Ras binding domain of PI-3-kinase: A quantitative approach to KD measurements

14 | Feb 02 2024

The developed approach combining UV spectral deconvolution, HPLC, and microscale thermophoresis quantifies the KD for binding between active Ras and PI3K, revealing how specific Ras mutations at PI3K contact positions can significantly alter binding affinity and potentially impact cellular signaling and disease pathways. [Read the Full Post]

Discovery of potent DNMT1 inhibitors against sickle cell disease using structural-based virtual screening, MM-GBSA and molecular dynamics simulation-based approaches

20 | Jan 25 2024

The study's rigorous virtual screening and molecular dynamics simulations identified promising compounds with potential to inhibit DNMT1, offering a hopeful avenue for improving sickle cell disease treatment pending further in vitro and in vivo validation. [Read the Full Post]

MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer

15 | Jan 24 2024

MRTX1719, a selective PRMT5 inhibitor, displays remarkable efficacy against MTAP-deleted cancers while sparing MTAP wild-type cells, showcasing promising therapeutic potential and early clinical success across a spectrum of malignancies. [Read the Full Post]

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

54 | Jan 23 2024

Isolinderalactone demonstrates significant potential as a therapeutic agent for colorectal cancer by inducing G2/M phase arrest, apoptosis, autophagy, and MAPK pathway activation via ROS-mediated signaling in human CRC cells. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

62 | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer

23 | Jan 20 2024

CTx-648, a highly potent and selective KAT6A/KAT6B inhibitor, demonstrates significant anti-tumor activity in ER-positive breast cancer models, including those resistant to endocrine therapy, showing promise for targeting KAT6A in this context. [Read the Full Post]

JAK2 Inhibitor, Fedratinib, Inhibits P-gp Activity and Co-Treatment Induces Cytotoxicity in Antimitotic Drug-Treated P-gp Overexpressing Resistant KBV20C Cancer Cells

34 | Jan 17 2024

Fedratinib's combination with vincristine demonstrates promising cytotoxicity specifically in P-glycoprotein-overexpressing drug-resistant cancer cells, suggesting its potential as an effective co-treatment strategy for multidrug-resistant cancers. [Read the Full Post]

Immunotherapies against HER2-Positive Breast Cancer

21 | Jan 14 2024

Immunotherapy offers a promising array of strategies, from cancer vaccines to immune checkpoint blockade and adoptive cell therapy, holding the potential to transform the treatment landscape for HER2-positive breast cancer by enhancing immune responses and potentially preventing disease progression. [Read the Full Post]

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

43 | Jan 11 2024

This comprehensive review highlights the evolving landscape of JAK inhibitors in myelofibrosis treatment, emphasizing their varying efficacy in addressing symptoms and the need for further studies to ascertain their precise impact and facilitate more personalized therapeutic approaches. [Read the Full Post]

In silico and in vitro human metabolism of IOX2, a performance-enhancing doping agent

21 | Jan 10 2024

The study successfully identified thirteen metabolites of IOX2 in human hepatocytes, with hydroxyquinolinyl-IOX2 emerging as a major biomarker, emphasizing the critical role of glucuronide hydrolysis for enhanced detectability in urine, offering valuable insights for anti-doping testing. [Read the Full Post]

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles

0 | Jan 10 2024

The discovery of aurora kinase inhibitors significantly impairing HSV-1 gene expression and replication, while also impacting other viral families, illuminates a promising avenue for broad-spectrum antiviral therapies targeting these pivotal cellular kinases. [Read the Full Post]

The mitochondrial NADH shuttle system is a targetable vulnerability for Group 3 medulloblastoma in a hypoxic microenvironment

25 | Jan 08 2024

Research examining metabolic pathways in Group 3 medulloblastoma cells has unveiled promising therapeutic strategies, showcasing inhibitors that target NADH shuttles and mitochondrial function, offering hope for more effective treatments in this aggressive tumor subtype. [Read the Full Post]

Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

99 | Jan 06 2024

Sertad1, upregulated in ischemic conditions, exacerbates neurological injury by activating the CDK4/p-Rb pathway, promoting cell cycle dysregulation and apoptotic cell death. [Read the Full Post]

Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation

31 | Jan 06 2024

The study delineates TUFT1's pivotal role in hepatocellular carcinoma (HCC) progression by elucidating its influence on lipid metabolism, cell proliferation through CREB1 interaction, and invasion via modulation of zyxin expression and recruitment to focal complexes in HCC cells. [Read the Full Post]

Utilization of AlphaFold models for drug discovery: Feasibility and challenges. Histone deacetylase 11 as a case study

58 | Jan 04 2024

Your study on optimizing the HDAC11 AlphaFold model, validating it through molecular dynamics simulations and successful docking of known inhibitors, provides a promising foundation for structure-based drug design targeting HDAC11. [Read the Full Post]

Inhibiting CBX4 efficiently protects hepatocellular carcinoma cells against sorafenib resistance

14 | Jan 03 2024

Blocking CBX4 expression appears pivotal in addressing sorafenib resistance in advanced hepatocellular carcinoma, with miR424 and its suppression of CBX4 revealing potential therapeutic avenues. [Read the Full Post]

Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection

0 | Jan 03 2024

ML324 demonstrates significant potential as an effective treatment against Cyprinid herpesvirus 3 (CyHV-3) infection in koi fish, outperforming traditional antiviral drugs like acyclovir in inhibiting virus replication both in vitro and in vivo. [Read the Full Post]

Epigenetic Compound Screening Uncovers Small Molecules for Reactivation of Latent HIV-1

62 | Jan 02 2024

The study utilized a cell-based reporter system under BSL-1 conditions to screen an epigenetic compound library, identifying two promising compounds, HPOB and SR-4370, with high reactivation efficiencies and low toxicity, offering potential as effective treatments for reversing HIV-1 latency. [Read the Full Post]

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A

13 | Jan 01 2024

The study on Withania somnifera compounds demonstrates promising anticancer potential through molecular interactions with KAT6A and validated inhibitory effects on human breast cancer cells, validating the traditional use of W. somnifera as an effective anticancer herb. [Read the Full Post]

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development

47 | Dec 31 2023

The iterative development of a population pharmacokinetic model for ritlecitinib, integrating data from diverse clinical trials, culminated in a refined two-compartment model with direct-response non-stationary clearance, informing critical clinical decisions and shaping the drug's label across varied conditions. [Read the Full Post]

Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue

108 | Dec 28 2023

Parthenolide treatment in rats demonstrated a dose-dependent mitigation of oxidative stress-induced testicular damage caused by paclitaxel, showing promise as a potential therapeutic avenue for addressing testicular toxicity and supporting reproductive function. [Read the Full Post]

LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression

16 | Dec 28 2023

The HOTAIR/miR-145-5p/NUAK1 axis, identified through its intricate epigenetic regulation and influence on the EMT process in liver cancer cells, holds promise as both a prognostic biomarker and a potential therapeutic target. [Read the Full Post]

Research update and opportunity of non-hormonal male contraception: Histone demethylase KDM5B-based targeting

16 | Dec 27 2023

In exploring non-hormonal male contraceptives, leveraging in-silico studies of tissue-specific targets and small-molecule candidates presents a promising avenue, albeit with hurdles, toward potentially transformative developments in contraceptive options. [Read the Full Post]

Conformational-Design-Driven Discovery of EZM0414: A Selective, Potent SETD2 Inhibitor for Clinical Studies

38 | Dec 25 2023

The evolution from a novel SETD2 inhibitor tool compound to the potent and orally bioavailable EZM0414 marks a significant achievement in drug development, promising potential clinical implications for conditions like multiple myeloma featuring a t(4,14) translocation. [Read the Full Post]

CPI-203 improves the efficacy of anti-PD-1 therapy by inhibiting the induced PD-L1 overexpression in liver cancer

32 | Dec 24 2023

The study's use of CPI-203, a BRD4 inhibitor, in conjunction with PD-1 antibodies shows promising potential to overcome PD-L1-mediated resistance to immunotherapy in hepatocellular carcinoma. [Read the Full Post]

NHWD-870 protects the kidney from ischemia/reperfusion injury by upregulating the PI3K/AKT signaling pathway (experimental study)

48 | Dec 23 2023

NHWD-870 exhibits substantial nephroprotective effects by attenuating renal damage through its anti-apoptotic, anti-inflammatory, and antioxidant properties, indicating potential therapeutic promise in managing renal ischemia-reperfusion injury. [Read the Full Post]

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin

62 | Dec 22 2023

High SLFN11 expression, identified as a top prognostic marker, is associated with longer survival in WNT-activated and a subset of SHH-activated medulloblastomas, possibly through enhanced sensitivity to DNA damaging agents such as cisplatin, with pharmacological upregulation by RG2833 showing promise for therapeutic intervention. [Read the Full Post]

Medicare's Hospital Readmission Reduction Program reduced fall-related health care use: An unexpected benefit?

16 | Dec 21 2023

The study found that Medicare's Hospital Readmissions Reduction Program (HRRP) was associated with significant reductions in severe fall-related injuries, particularly for congestive heart failure and pneumonia patients, indicating potential improvements in transitional care and post-acute referral patterns. [Read the Full Post]

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis

38 | Dec 20 2023

This study reveals altered immune cell infiltration, identifies key signaling pathways, and proposes potential diagnostic markers and therapeutic compounds for recurrent implantation failure, offering valuable insights for improving endometrial receptivity in reproductive medicine. [Read the Full Post]

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

36 | Dec 18 2023

Pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, demonstrates immunomodulatory effects by inhibiting myeloid-derived suppressor cells (MDSCs) and Th17 cell-mediated inflammation, making it a promising candidate for the treatment of multiple sclerosis and other autoimmune diseases. [Read the Full Post]

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells

51 | Dec 14 2023

The study demonstrates that aurora kinase inhibitors, particularly reversine, exert significant antineoplastic effects in Ba/F3 cells expressing the CSF3RT618I mutation, reducing cell viability, clonogenicity, and proliferative capacity, while modulating key molecular pathways associated with cell cycle and apoptosis in the context of chronic neutrophilic leukemia (CNL). [Read the Full Post]

Increased recombinant adeno-associated virus production by HEK293 cells using small molecule chemical additives

23 | Dec 09 2023

The study demonstrates that the addition of small molecule bioactive chemical additives, nocodazole and M344, significantly enhances rAAV vector production in HEK cells, increasing genome titre up to three-fold and indicating a promising approach for improving the cost-effectiveness of gene therapy production processes. [Read the Full Post]

Cantharidin induces senescence via inhibition of AMP-activated protein kinase and activation of NLRP3 inflammasome in H9c2 cardiomyocytes

13 | Dec 07 2023

Cantharidin induces cardiomyocyte senescence and senescence-associated secretory phenotype (SASP) through activation of the NLRP3 inflammasome and inhibition of AMPK phosphorylation, providing novel insights into its cardiotoxic effects. [Read the Full Post]

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells

38 | Dec 06 2023

**In Jak2V617F positive classical myeloproliferative neoplasms, aberrant activation of Stat5a downregulates Dnmt3a through binding to its promoter, leading to dysregulation of the miR-17-5p/Cdkn1a axis and G0/G1 cell cycle arrest, providing a potential therapeutic target.** [Read the Full Post]

Effect of feed enriched by products formulated from coconut water, palm sap sugar, and mushroom on the chemical composition of feed and carcass, growth performance, body indices, and gut micromorphology of giant gourami, Osphronemus goramy (Lacepède, 1801), juveniles

18 | Dec 05 2023

The study found that the formulation KP3, incorporating palm sap sugar, coconut water, and specific microorganisms, significantly improved the nutrition, growth, and body composition of giant gourami juveniles, making it a promising option for aquaculture in Indonesia. [Read the Full Post]

Daprodustat: A potential game-changer in renal anemia therapy-A perspective

27 | Dec 04 2023

As of my last update in September 2021, I cannot confirm the recent FDA approval of daprodustat (DPD) for anemia due to chronic kidney disease in dialysis patients or its potential applications in non-dialysis patients and those with coexisting renal anemia and heart failure; for the latest information, please refer to official sources. [Read the Full Post]

ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway

18 | Dec 02 2023

ALKBH5 upregulation in age-related macular degeneration leads to retinal pigment epithelium dysfunction and choroidal neovascularization through its demethylation activity, activating the PIK3C2B-mediated AKT/mTOR pathway, and pharmacological inhibitors like IOX1 offer potential therapeutic interventions. [Read the Full Post]

HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice

45 | Dec 01 2023

BRD3308 (BRD), an inhibitor of histone deacetylase 3 (HDAC3), reduces neuroinflammation, inhibits pyroptosis, and improves neurobehavioral outcomes in a mouse model of intraventricular hemorrhage by activating the PPARγ/NLRP3/GSDMD signaling pathway. [Read the Full Post]

Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

35 | Nov 30 2023

The study investigated the dysregulation of cancer-related circular RNAs (circRNAs) and their linear transcripts (linRNAs) in breast cancer cell lines exposed to various anticancer drugs, revealing altered circRNA/linRNA expression ratios and identifying specific circRNAs associated with apoptosis, cell migration, and mutated pathways, thereby shedding light on their potential roles as biomarkers and therapeutic targets in breast cancer treatment. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

103 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Phase 1 Results of Bromodomain and Extraterminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies

23 | Nov 25 2023

In a phase I trial, the combination therapy of PLX51107 (a bromodomain and extra-terminal domain inhibitor) and azacitidine demonstrated a 22% overall response rate and significant changes in gene and protein expressions, providing modest clinical benefit in heavily pre-treated patients with relapsed/refractory high-risk myelodysplastic syndrome and acute myeloid leukemia. [Read the Full Post]

Carnosic acid and rosemary extract reversed the lipid accumulation induced by bisphenol A in the 3T3-L1 preadipocytes and C57BL/6J mice via SIRT1/FoxO1 pathway

32 | Nov 23 2023

Carnosic acid (CA) and rosemary extract counteracted Bisphenol A (BPA)-induced adipogenesis and lipid accumulation by downregulating adipogenic proteins, upregulating lipolytic proteins, and activating the SIRT1/FoxO1 pathway in both 3T3-L1 preadipocytes and C57BL/6 J mice. [Read the Full Post]

Ginkgolic acid inhibits the replication of pseudorabies virus in vitro and in vivo by suppressing the transcription of viral late genes

35 | Nov 22 2023

Ginkgolic acid has been identified as a potent inhibitor of pseudorabies virus (PRV) replication by specifically suppressing the transcription of PRV late genes, offering a promising therapeutic avenue for combating PRV infections in the swine industry. [Read the Full Post]

Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma

34 | Nov 20 2023

The study demonstrates that inhibiting lysine-specific demethylase 1 (LSD1) synergizes with proteasome inhibitors, such as carfilzomib, overcoming drug resistance in multiple myeloma and other B-cell malignancies, offering a promising therapeutic strategy. [Read the Full Post]

Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells

23 | Nov 19 2023

Inhibiting SETD7 catalytic activity using (R)-PFI-2 disrupts mammary epithelial cell differentiation by increasing proliferation, downregulating differentiation markers, and altering lipid metabolism. [Read the Full Post]

Androgen Receptor Variants Confer Castration Resistance in Prostate Cancer by Counteracting Antiandrogen-Induced Ferroptosis

23 | Nov 19 2023

The passage discusses how acute treatment with the antiandrogen enzalutamide induces ferroptosis in prostate cancer cells by decreasing glutathione production, increasing lipid peroxidation, and upregulating the cystine transporter gene SLC7A11 through both full-length and variant forms of the androgen receptor, revealing a potential mechanism for therapeutic resistance and identifying a target for intervention. [Read the Full Post]

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

95 | Nov 17 2023

Meticrane, a non-oncology drug originally used to treat hypertension, exhibits promising anti-cancer effects on leukemia and liver cancer cells, including synergistic interactions with epigenetic inhibitors, alterations in gene expression associated with non-cancer pathways, and considerable binding affinity to key cancer-related proteins, although it does not enhance the cytotoxicity of cytokine-induced killer cells, suggesting its potential as a novel cancer therapy warrants further investigation. [Read the Full Post]

PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc

34 | Nov 16 2023

The study identifies PHA-680626 as a dual-function inhibitor capable of disrupting the AURKA/N-Myc interaction, offering a promising therapeutic strategy for treating neuroblastoma by destabilizing this oncogenic complex. [Read the Full Post]

Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection

51 | Nov 16 2023

ML324, a specific inhibitor of JMJD2 histone demethylase, has demonstrated promising potential as a treatment against CyHV-3 infection in koi fish, effectively inhibiting viral replication both in vitro and in vivo. [Read the Full Post]

IL-17 Is a Key Regulator of Mucin-Galectin-3 Interactions in Asthma

48 | Nov 15 2023

Galectin-3 (Gal-3) appears to play a pivotal role in the pathogenesis of asthma by regulating airway inflammation and mucin gene expression, suggesting that targeting Gal-3 could be a promising therapeutic strategy for the disease. [Read the Full Post]

Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003

17 | Nov 14 2023

NUAK1 and NUAK2 promote cell survival and proliferation in prostate stromal cells, potentially contributing to stromal hyperplasia in benign prostatic hyperplasia (BPH), and their effects can be mimicked by inhibitors HTH01-015 and WZ4003, suggesting therapeutic relevance in BPH management. [Read the Full Post]

Deciphering the Allosteric Activation Mechanism of SIRT6 Using Molecular Dynamics Simulations

52 | Nov 13 2023

This study proposes a mechanism where myristic acid and synthetic SIRT6 activators stabilize NAD+ binding and substrate interactions, shedding light on SIRT6 activation and offering insights for the design of potential therapeutic agents. [Read the Full Post]

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2

107 | Nov 12 2023

The research reveals that tumor-associated astrocytes (TAAs) secrete lipocalin-2 (LCN2) through the STAT3 signaling pathway, promoting the progression of Sonic Hedgehog (SHH) subgroup medulloblastoma (MB) and indicating LCN2's potential as a prognostic marker and therapeutic target. [Read the Full Post]

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study

64 | Nov 12 2023

The study provided evidence that a lower-dose rituximab (RTX) therapy strategy is effective and safe in treating neuromyelitis optica spectrum disorder (NMOSD), potentially changing the approach to NMOSD treatment by addressing optimal dosage and therapy initiation timing. [Read the Full Post]

The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells

0 | Nov 10 2023

A1874, a novel BRD4-degrading PROTAC, demonstrates potent anti-colon cancer activity through both BRD4-dependent and -independent mechanisms, inhibiting cell growth, inducing apoptosis, and showing efficacy in in vivo models. [Read the Full Post]

Staphylococcus aureus Infection Initiates Hypoxia-Mediated Transforming Growth Factor-β1 Upregulation to Trigger Osteomyelitis

61 | Nov 09 2023

This study reveals a novel signaling cascade involving hypoxia/HIF-1α/TGF-β1 in the pathogenesis of Staphylococcus aureus-induced osteomyelitis, highlighting its potential as a therapeutic target for the condition. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

0 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

Novel small molecule inhibitors of the transcription factor ETS-1 and their antitumor activity against hepatocellular carcinoma

18 | Nov 08 2023

This study identified four novel small molecule inhibitors of the transcription factor ETS-1, demonstrating their potential to suppress HCC cell proliferation and invasion, offering safer and more effective therapeutic strategies for hepatocellular carcinoma. [Read the Full Post]

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer

12 | Nov 03 2023

This study found that the effectiveness of chemotherapy agents varied in platinum-resistant ovarian cancer patients based on tumor characteristics, such as histological type and platinum-free interval, as well as the use of bevacizumab. [Read the Full Post]

Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer

56 | Oct 29 2023

HDAC inhibitors in breast cancer have demonstrated potent anti-tumor activity and the potential to improve immunotherapy outcomes, highlighting their potential as potent agents to enhance breast cancer treatment. [Read the Full Post]

Synthesis and biological evaluation of novel N-benzyltriazolyl-hydroxamate derivatives as selective histone deacetylase 6 inhibitors

52 | Oct 27 2023

The study designed and evaluated a novel N-benzyltriazolyl-hydroxamate scaffold, resulting in the identification of compound 4u as a highly potent and selective HDAC6 inhibitor, providing insights for the development of targeted therapies for neurodegenerative diseases, inflammation, and cancer. [Read the Full Post]

Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis

22 | Oct 25 2023

This study revealed metabolomic reprogramming in early hyperlipidemia, characterized by upregulated metabolites promoting trained immunity, uremic toxins, and proatherogenic metabolites, while highlighting the suppressive role of the antioxidant transcription factor NRF2 in this process. [Read the Full Post]

The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study

34 | Oct 25 2023

The combination of iodine-131 with topoisomerase I and PARP inhibitors demonstrated marked effects in sensitizing glioblastoma cells to radiotherapy, indicating its potential as a targeted radionuclide therapy to enhance treatment efficacy. [Read the Full Post]

Relationship among cattle breed and anabolic implant protocol relative to feedlot performance: Growth, temperament, feeding behavior, carcass traits, and economic return

42 | Oct 24 2023

The study found that a moderate intensity anabolic implant protocol was optimal for feedlot steers of different breed types, resulting in increased average daily gain and higher net return per head compared to non-implanted and high intensity implant groups in a temperate climate. [Read the Full Post]

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]

39 | Oct 24 2023

Bempedoic acid, a newly approved therapeutic option for hypercholesterolemia, offers a hepatic selective action that reduces the risk of muscle adverse effects, making it particularly useful in certain clinical settings according to an ANMCO document. [Read the Full Post]

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B cell lymphoma

31 | Oct 24 2023

The study identifies EGR1-mediated metabolic reprogramming to oxidative phosphorylation as a key mechanism driving ibrutinib resistance in B cell malignancies, suggesting that targeting this pathway with agents like metformin or IM156 could provide a potential therapeutic strategy to overcome acquired drug resistance in relapsed/refractory DLBCL or MCL. [Read the Full Post]

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

88 | Oct 23 2023

Stenoparib (2X-121), a poly (ADP-ribose) polymerase (PARP) inhibitor, demonstrates effective inhibition of SARS-CoV-2 and its variant strains in vitro, with the potential for enhanced antiviral activity when combined with remdesivir. [Read the Full Post]

Inhibition of HDAC6 With CAY10603 Ameliorates Diabetic Kidney Disease by Suppressing NLRP3 Inflammasome

67 | Oct 22 2023

The study identified CAY10603, an HDAC6 inhibitor, as a potential therapeutic drug for diabetic nephropathy by suppressing NLRP3 inflammasome activation in tubular cells and macrophages. [Read the Full Post]

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

39 | Oct 21 2023

SIRT6, through its regulation of the ERK1/2 pathway and enhancement of autophagy, demonstrates a beneficial role in acute respiratory distress syndrome (ARDS) by ameliorating tight junction protein loss, inflammation, and apoptosis, suggesting its potential as a therapeutic target for ARDS. [Read the Full Post]

AURKB Enhances Chromosomal Remodeling of Telomeric Genes and Accelerates Tumorigenesis of Uveal Melanoma

29 | Oct 18 2023

AURKB inhibitors show promise as a therapeutic strategy for uveal melanoma by epigenetically silencing the expression of the oncogenic telomerase reverse transcriptase (TERT). [Read the Full Post]

Porcine cardiac blood - Salvia miltiorrhiza root alleviates cerebral ischemia reperfusion injury by inhibiting oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway

46 | Oct 17 2023

PCB-DS, a combination of Salvia miltiorrhiza and porcine cardiac blood, alleviates cerebral ischemia/reperfusion injury (CIRI) by inhibiting oxidative stress-induced apoptosis through the PI3K/AKT/Bcl-2/Bax signaling pathway. [Read the Full Post]

Knockdown screening of chromatin binding and regulatory proteins in zebrafish identified Suz12b as a regulator of tfpia and an antithrombotic drug target

82 | Oct 15 2023

This study identified novel epigenetic regulators of the tfpia gene and demonstrated the potential of UNC6852 as an antithrombotic drug by enhancing tfpia mRNA levels and prolonging the time to occlude the caudal vessel after laser injury in zebrafish larvae and adults. [Read the Full Post]

Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration

28 | Oct 12 2023

Elevated levels of HTRA1 in age-related macular degeneration (AMD) contribute to retinal pigment epithelium (RPE) senescence by damaging mitochondrial function and activating HIF-1 signaling, suggesting the inhibition of HIF-1 signaling as a potential therapeutic strategy for AMD. [Read the Full Post]

PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism

65 | Oct 11 2023

PRMT3 promotes the progression of glioblastoma by enhancing HIF1α-mediated glycolysis and metabolic rewiring, presenting a potential therapeutic target for treating malignant gliomas. [Read the Full Post]

Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia

30 | Oct 09 2023

Defective cell cycle arrest, particularly involving downregulation of CDKN2A, is a clinically significant contributor to chemoresistance in acute myeloid leukemia (AML), and therapeutic combinations targeting the G1S cell cycle restriction point and promoting apoptosis show promise in enhancing treatment response and potentially overcoming chemoresistance. [Read the Full Post]

The histone acetyltransferase Mof regulates Runx2 and Osterix for osteoblast differentiation

22 | Oct 08 2023

The study reveals that the histone acetyltransferase Mof functions as a novel regulator of osteoblast differentiation by promoting the expression of osteogenic markers Runx2 and Osterix, suggesting its potential as a therapeutic target for conditions like osteosarcoma and osteoporosis. [Read the Full Post]

The Functional Role and Regulatory Mechanism of FTO m6A RNA Demethylase in Human Uterine Leiomyosarcoma

70 | Oct 08 2023

In summary, the study highlights the aberrant upregulation of FTO m6A RNA demethylase in uterine leiomyosarcoma tissues and demonstrates that inhibiting FTO with Dac51 can significantly decrease uLMS cell proliferation, modulate key pathways, and potentially offer a novel therapeutic strategy for this aggressive uterine cancer. [Read the Full Post]

SIRT5 IS A DRUGGABLE METABOLIC VULNERABILITY IN ACUTE MYELOID LEUKEMIA

60 | Oct 08 2023

The discovery that the survival and growth of AML cells, irrespective of their genetic characteristics, rely on SIRT5 highlights its potential as a therapeutic target for AML treatment. [Read the Full Post]

Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells

73 | Oct 07 2023

The study found that prolonged exposure of ER+ MCF-7 breast cancer cells to tamoxifen led to increased expression of the ABCG2 pump, associated with TAM resistance and potential cross-resistance to mitoxantrone. [Read the Full Post]

BRD9 is an essential regulator of glycolysis that creates an epigenetic vulnerability in colon adenocarcinoma

50 | Sep 29 2023

The study revealed that BRD9 plays important roles in colon cancer metabolism and tumor progression, highlighting its potential as a valuable therapeutic target for patients with colon cancer (COAD). [Read the Full Post]

Bone impact after two years of low-dose oral contraceptive use during adolescence

62 | Sep 29 2023

The present study indicates that the use of combined hormonal contraceptives in healthy adolescents is associated with compromised bone mass acquisition, with a more pronounced negative impact observed in those using contraceptives containing 30 μg of Ethinylestradiol. [Read the Full Post]

Targeting homologous recombination deficiency in uterine leiomyosarcoma

20 | Sep 25 2023

This report highlights the significance of identifying homologous recombination deficiency in uterine leiomyosarcoma (uLMS) for therapeutic targeting with poly (ADP-ribose) polymerase (PARP) inhibitors and platinum agents, demonstrating encouraging clinical responses and suggesting the potential for PARP1-specific PARP inhibitors in future trials. [Read the Full Post]

The potent AMPK inhibitor BAY-3827 shows strong efficacy in androgen-dependent prostate cancer models

52 | Sep 24 2023

The novel and potent AMPK inhibitor BAY-3827 demonstrates strong anti-proliferative effects in androgen-dependent prostate cancer cell lines, upregulates genes involved in lipid metabolism, and inhibits key components of the lipid flux pathway, providing valuable insights into the role of AMPK signaling in cancer, especially in prostate cancer. [Read the Full Post]

Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells

96 | Sep 21 2023

The study validated the synergistic effect of combining a selective MET inhibitor (HS10241) with a PARP inhibitor (HS10160) in eliminating triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC) cells, suggesting its potential benefit for patients resistant to single-agent PARP inhibitor treatment. [Read the Full Post]

Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction

19 | Sep 20 2023

NHWD-870, a potent BET inhibitor, shows superior efficacy to current clinical stage inhibitors, suppressing tumor growth by downregulating c-MYC, inhibiting tumor cell proliferation, and blocking TAM proliferation through the suppression of CSF1 expression mediated by BRD4 inhibition and its target HIF1α. [Read the Full Post]

Guidance on the management of adverse reactions induced by poly(ADP-ribose) polymerase inhibitors

103 | Sep 20 2023

The common adverse reactions of PARP inhibitors, including hematological toxicity, gastrointestinal toxicity, and fatigue, can be managed through measures such as regular blood tests, referral to specialists, symptomatic treatment, and monitoring for potential complications. [Read the Full Post]

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors

65 | Sep 19 2023

Selective TYK2 inhibitors, such as deucravacitinib and ropsacitinib, offer a promising approach for treating inflammatory and autoimmune diseases with improved efficacy and safety profiles compared to broad JAK inhibitors. [Read the Full Post]

Mining the transcriptome of target tissues of autoimmune and degenerative pancreatic β-cell and brain diseases to discover therapies

17 | Sep 19 2023

The study identified shared inflammatory gene signatures between pancreatic β-cells in diabetes and neuronal tissue in multiple sclerosis and Alzheimer's disease, and demonstrated the potential of bromodomain inhibitors as therapeutic candidates to revert these transcriptional signatures. [Read the Full Post]

Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis

36 | Sep 18 2023

The systematic review and network meta-analysis found that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) did not significantly differ from erythropoiesis-stimulating agents (ESAs) in terms of overall adverse events and serious adverse events, but differences were observed in gastrointestinal disorder, hypertension, vascular-access complications, and hemoglobin response. [Read the Full Post]

Acetylation regulates the nucleocytoplasmic distribution and oncogenic function of karyopherin alpha 2 in lung adenocarcinoma

92 | Sep 18 2023

The acetylation of KPNA2 by CBP/p300 promotes cytosolic localization and suppresses its oncogenic activity in lung cancer cells. [Read the Full Post]

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors

75 | Sep 18 2023

Deucravacitinib, an allosteric tyrosine kinase 2 inhibitor, has been approved as a first-in-class treatment for moderate-to-severe plaque psoriasis and shows improved safety compared to orthosteric Janus kinase inhibitors. [Read the Full Post]

Evaluation of Drug-Drug Interaction Potential of Enarodustat (JTZ-951) Using a Cytochrome P450 Probe Cocktail

66 | Sep 17 2023

Enarodustat, administered at doses of 25 mg and 50 mg, showed minimal to no significant drug interactions with cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 in a phase 1 multiple-ascending-dose study, with changes in geometric mean ratios generally being less than 2-fold. [Read the Full Post]

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1

20 | Sep 15 2023

Pre-clinical studies demonstrate that monotherapy with a Menin inhibitor (MI) induces clinical remissions in some relapsed/refractory AML patients, but the combination of MI with inhibitors targeting BRD4, MOZ, LSD1, or CBP/p300 shows synergistic effects and superior efficacy, suggesting potential strategies to overcome therapy resistance and prevent relapse. [Read the Full Post]

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

75 | Sep 11 2023

This study reveals that norepinephrine, acting through the β2-adrenergic receptor, promotes Pseudomonas aeruginosa keratitis during contact lens wear, suggesting potential therapeutic targets for treating the condition. [Read the Full Post]

Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia

32 | Sep 10 2023

This study utilizes automated chromatin profiling techniques to map fusion-specific targets of KMT2A oncofusion proteins, revealing aberrant chromatin regulation and potential therapeutic vulnerabilities in acute myeloid and lymphoid leukemias. [Read the Full Post]

Dual inhibition of EZH1/2 induces cell cycle arrest of B cell acute lymphoblastic leukemia cells through upregulation of CDKN1C and TP53INP1

92 | Sep 09 2023

The study demonstrates that the EZH1/2 dual inhibitor DS-3201 (valemetostat) shows significant antitumor effects against B cell acute lymphoblastic leukemia (B-ALL) by inhibiting cell growth, inducing cell cycle arrest and apoptosis, and upregulating CDKN1C and TP53INP1 expression, offering a potential treatment option for B-ALL. [Read the Full Post]

UHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma

15 | Sep 08 2023

The study identified EZH2 as a master regulator of cellular heterogeneity in melanoma, specifically in relation to melanin pigment content, and proposed targeting the UHRF1/UBE2L6/UBR4-mediated regulation of EZH2 as a potential strategy for modulating its activity in melanoma cells. [Read the Full Post]

Two is company, is three a crowd? Triplet therapy, novel molecular targets, and updates on the management of advanced renal cell carcinoma

68 | Sep 06 2023

Recent advances in the management of advanced renal cell carcinoma include the favorability of nivolumab plus cabozantinib in combination therapy, promising results from triplet therapy and HIF-2α inhibitors, investigation of metabolic pathway inhibitors and biomarkers, and the ongoing evaluation of cytoreductive nephrectomy in the context of combination therapy. [Read the Full Post]

Effects of the inclusion of coffee pulp silage in the diet on the performance and profitability of crossbred milk cows in the middle tropics

44 | Sep 06 2023

The inclusion of coffee pulp silage in the diet of crossbred dairy cows in the middle tropics improved their productive efficiency and nutritional characteristics without affecting milk production. [Read the Full Post]

Deuterium in drug discovery: progress, opportunities and challenges

111 | Sep 05 2023

Deuteration, the substitution of a hydrogen atom with its heavy isotope deuterium, has emerged as a promising strategy in drug discovery and development, offering the potential to enhance drug efficacy and safety through improved pharmacokinetic and toxicity profiles. [Read the Full Post]

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis

81 | Sep 05 2023

Deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe psoriasis based on a systematic review and meta-analysis of randomized controlled trials. [Read the Full Post]

[LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5]

20 | Sep 05 2023

LLY-283, by inhibiting PRMT5 expression, effectively suppresses the proliferation and metastasis of Head and Neck Squamous Cell Carcinoma (HNSCC) and reduces tumor growth in vivo. [Read the Full Post]

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors

24 | Sep 03 2023

The Phase 1 study of GSK3368715, a reversible inhibitor of type I protein methyltransferases, was terminated early due to a higher-than-expected incidence of thromboembolic events, limited target engagement at lower doses, and lack of observed clinical efficacy. [Read the Full Post]

Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss

25 | Sep 03 2023

GSK3368715, a potent type I PRMT inhibitor, demonstrates anti-tumor effects and its combination with PRMT5 inhibition and consideration of MTAP status as a biomarker strategy show promise for effective oncology treatment. [Read the Full Post]

Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke

22 | Sep 01 2023

In this nationwide study, baseline antiplatelet treatment prior to mechanical thrombectomy for acute ischemic stroke did not improve functional independence or increase the risk of intracranial hemorrhage. [Read the Full Post]

Synthesis, Characterization, Antimicrobial Properties, and Antioxidant Activities of Silver-N-Heterocyclic Carbene Complexes

16 | Sep 01 2023

The study describes the synthesis and characterization of silver-NHC complexes, which exhibit strong antibacterial activity and significant antioxidant properties, offering potential as effective and multifunctional antimicrobial agents. [Read the Full Post]

m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis

35 | Aug 31 2023

The upregulation of the m6A mRNA demethylase FTO in radioresistant nasopharyngeal carcinoma (NPC) promotes radiotherapy resistance by inhibiting radiation-induced ferroptosis, suggesting FTO as a potential therapeutic target and prognostic biomarker for NPC. [Read the Full Post]

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

56 | Aug 28 2023

The phase IIb study showed that brepocitinib at doses of 30 mg and 60 mg once daily (QD) was more effective than placebo in reducing symptoms of psoriatic arthritis (PsA) and demonstrated a favorable safety profile throughout the 52-week study. [Read the Full Post]

Inhibiting Histone and DNA Methylation Improves Cancer Vaccination in an Experimental Model of Melanoma

28 | Aug 28 2023

The study demonstrated that a dual inhibitor targeting histone methyltransferase G9a and DNA methyltransferases (DNMTs) induced tumor cell cycle arrest, apoptosis, and an IFN-I response, while promoting dendritic cell and T-cell infiltration, ultimately increasing the overall survival of mice with melanoma in combination with TCR-redirected T-cell therapy and dendritic cell vaccination. [Read the Full Post]

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

40 | Aug 26 2023

AK-01, a highly selective AURKA inhibitor, demonstrates potent tumor suppression through apoptosis and cell cycle arrest in MCPyV-negative Merkel cell carcinoma cells without RB expression, highlighting its potential as a promising therapeutic option for MCC management. [Read the Full Post]

The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage

74 | Aug 25 2023

The study demonstrates that targeted degradation of BET proteins using dBET6 effectively inhibits the cGAS-STING pathway in reactive retinal macrophages/microglia, providing neuroprotective effects and suggesting a potential therapeutic approach for retinal degenerative diseases. [Read the Full Post]

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary

37 | Aug 25 2023

The summary discusses a clinical study that found abrocitinib to be more effective than dupilumab in quickly improving the signs and symptoms of moderate to severe atopic dermatitis (AD) in individuals who did not respond to prescribed topical medications. [Read the Full Post]

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

109 | Aug 25 2023

This meta-analysis suggests that abrocitinib is both safe and effective in treating moderate-to-severe atopic dermatitis in adolescents and adults, with the 200 mg dose showing a greater efficacy compared to the 100 mg dose. [Read the Full Post]

Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers And Guide Surgical Decision Making

36 | Aug 23 2023

This study presents an efficient method for performing fluorescein angiography during Digitally Assisted Vitreoretinal Surgery, enabling real-time visualization and intervention by modifying the accessory light sources and utilizing digital imaging software. [Read the Full Post]

Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of Clinical Trials

57 | Aug 23 2023

The evaluation of twelve BET inhibitors in clinical trials for hematological malignancies and solid tumors revealed common hematological and non-hematological adverse events, moderate efficacy rates, and the need for further investigation into dosing schemes and combination therapies to enhance their therapeutic potential. [Read the Full Post]

Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens

61 | Aug 22 2023

The study revealed that deficiency of the SPOP gene leads to significant resistance to BET inhibitors (BETi), and a combination therapy targeting both BET and GSK3 using ABBV-744 and CHIR-98014 showed promise in impeding the progression of KMT2A-rearranged leukemia. [Read the Full Post]

Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734

71 | Aug 19 2023

Combining selective p300/CBP and BET bromodomain inhibitors demonstrates potent inhibition of NMC growth, induction of cell differentiation, and improved survival in xenograft models, providing a strong rationale for clinical study of the dual inhibitor NEO2734 in patients with NMC. [Read the Full Post]

[Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy]

26 | Aug 18 2023

Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR signaling-mediated autophagy in cardiomyocytes. [Read the Full Post]

Development and clinical application of a liquid chromatography-tandem mass spectrometry-based assay to quantify eight tyrosine kinase inhibitors in human plasma

27 | Aug 18 2023

This study successfully developed and validated a sensitive LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma, demonstrating its potential clinical utility in therapeutic drug monitoring. [Read the Full Post]

Nicotinamide ameliorates mitochondria-related neuronal apoptosis and cognitive impairment via the NAD+/SIRT3 pathway

52 | Aug 16 2023

Nicotinamide (NAM) can alleviate neuronal apoptosis and microglial over-activation in a rat model of schizophrenia by modulating the NAD+-SIRT3-SOD2 signaling pathway, indicating its potential as a novel treatment approach for the disorder. [Read the Full Post]

JNJ-64619178 radiosensitizes and suppresses fractionated ionizing radiation-induced neuroendocrine differentiation (NED) in prostate cancer

55 | Aug 15 2023

The study demonstrates that JNJ-64619178 inhibits DNA damage repair, radiosensitizes prostate cancer cells, and suppresses FIR-induced neuroendocrine differentiation, suggesting its potential as a therapeutic agent for enhancing the effectiveness of radiation therapy in prostate cancer treatment. [Read the Full Post]

BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality

29 | Aug 13 2023

BRCAness refers to a tumor's homologous recombination repair defect, either through genetic inactivation of BRCA or HRD genes, and can be identified through genomic profiling, with implications for selecting targeted therapies such as PARP inhibitors, TOP1 inhibitors, and platinum derivatives. [Read the Full Post]

Advanced ovarian clear cell carcinoma with RAD50 mutation treated by PARP inhibitor pamiparib combined with anti-angiogenesis therapy: a case report

33 | Aug 13 2023

Targeted combination therapy with the PARP inhibitor pamiparib and bevacizumab showed promising results in achieving partial remission and improving the quality of life in a 45-year-old female patient with advanced ovarian clear cell carcinoma (OCCC) and a RAD50 mutation. [Read the Full Post]

HDAC inhibitor chidamide overcomes drug resistance in chronic myeloid leukemia with the T315i mutation through the Akt-autophagy pathway

113 | Aug 12 2023

Chidamide, a Histone Deacetylase Inhibitor (HDACi) drug, shows promising anti-leukemia effects and has the potential to overcome T315I mutation-related drug resistance in Chronic Myeloid Leukemia (CML) when used in combination with Tyrosine Kinase Inhibitors (TKIs). [Read the Full Post]

Second-line Endocrine Therapy of Hormone Receptor-Positive/HER2-negative Advanced Breast Cancer: A Systematic Review and Network Meta-analysis

58 | Aug 12 2023

The network meta-analysis found that cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with fulvestrant (Ful500) demonstrated the best progression-free survival (PFS) and overall survival (OS) outcomes as second-line therapy for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer, with palbociclib ranking first in terms of PFS and CDK4/6i ranking first in terms of OS. [Read the Full Post]

HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice

42 | Aug 07 2023

The study reveals that HDAC9 induction in renal tubular epithelial cells mediates G2/M cell cycle arrest, leading to tubulointerstitial fibrosis, and suggests HDAC9 as a potential therapeutic target for treating kidney fibrosis. [Read the Full Post]

Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro

17 | Aug 06 2023

The study demonstrated that EED226 treatment increased the survival of female germline stem cells (FGSCs), promoted their differentiation into oocytes, and suggested an effective culture strategy for in vitro oogenesis. [Read the Full Post]

Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer

0 | Aug 05 2023

The study demonstrates that the HDAC6 inhibitor ACY241 promotes favorable changes in the tumor immune microenvironment, enhancing T cell function and macrophage activation, and when combined with Oxaliplatin, it leads to significantly improved tumor-associated T cell effector functionality, suggesting its potential as a therapeutic intervention in non-small cell lung cancer (NSCLC). [Read the Full Post]

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

0 | Aug 05 2023

Co-inhibition of HDAC6 and HDAC8 with selective inhibitors synergistically suppresses cancer cell proliferation, enhances apoptosis, and inhibits metastasis in p53 wild-type ovarian cancer cells, indicating a potential novel therapeutic approach for ovarian cancer. [Read the Full Post]

Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control

49 | Aug 03 2023

This study identified multiple metabolites, including hydroxylated and glucuronic acid conjugated forms, for the hypoxia-inducible factor-prolyl hydroxylase inhibitor compounds BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes, shedding light on their metabolic pathways and potential misuse as performance enhancers. [Read the Full Post]

VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis

61 | Aug 03 2023

This study demonstrates the potential of VH298-loaded extracellular vesicles (EVs) and GelMA hydrogel as a promising therapeutic strategy for diabetic wound treatment, promoting angiogenesis and enhancing wound healing. [Read the Full Post]

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists

67 | Aug 02 2023

This review provides a practical guide for radiologists on the interpretation of liver disease using MRI and US, focusing on quantitative imaging biomarkers such as liver fibrosis, fat, and iron, and covering technical requirements, measurement techniques, case interpretation guidelines, and potential pitfalls. [Read the Full Post]

Mivebresib alleviates systemic lupus erythematosus-associated diffuse alveolar hemorrhage via inhibiting infiltration of monocytes and M1 polarization of macrophages

36 | Aug 01 2023

Mivebresib, a BRD4 inhibitor, demonstrates potential as a therapeutic option for diffuse alveolar hemorrhage associated with systemic lupus erythematosus by inhibiting macrophage polarization and inflammatory cell infiltration. [Read the Full Post]

Loss of VOPP1 Contributes to BET Inhibitor Acquired Resistance in Non-Small Cell Lung Cancer Cells

50 | Aug 01 2023

This study demonstrates that the loss of VOPP1 leads to the gain of BCL-2, resulting in resistance to BET inhibitors in non-small cell lung cancer, and suggests that combination therapy with BET inhibitors and BCL-2 inhibitors may overcome this resistance. [Read the Full Post]

HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans

16 | Jul 30 2023

This study demonstrated the successful inhibition of HIF2α and tumor suppression using a systemic, tumor-directed, RNA-silencing drug (siHIF2), providing a proof-of-principle for targeted RNA-based therapeutics in clear cell renal cell carcinomas (ccRCC). [Read the Full Post]

Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP)

33 | Jul 30 2023

The study demonstrates that PT2385, an oral specific HIF-2α inhibitor, shows promise in treating severe placental dysfunction associated with preeclampsia by enhancing cytotrophoblast differentiation, normalizing angiogenic factor secretion, and preventing the onset of maternal symptoms in an animal model. [Read the Full Post]

EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine

37 | Jul 30 2023

The study suggests that targeting the EZH2 histone methyltransferase with inhibitors like CPI-1205 and utilizing metformin may hold promise as potential therapeutic options for patients with small intestinal neuroendocrine tumors (SI-NETs). [Read the Full Post]

Prototropic forms of hydroxy derivatives of naphthoic acid within deep eutectic solvents

29 | Jul 29 2023

The prototropic behavior of probes in deep eutectic solvents (DESs) is strongly influenced by the varying hydrogen-bonding capabilities of the DES constituents, as observed through the presence or absence of specific prototropic forms of the probes in different DES compositions. [Read the Full Post]

BRD4: New hope in the battle against glioblastoma

17 | Jul 28 2023

This review provides a comprehensive overview of the roles and mechanisms of BRD4 in glioblastoma pathogenesis, as well as evaluates the potential of BRD4 inhibitors and degraders as novel treatment strategies against GBM. [Read the Full Post]

A high-concentrate diet induces inflammatory injury via regulating Ca2+/CaMKKβ-mediated autophagy in mammary gland tissue of dairy cows

52 | Jul 26 2023

The study found that a high-concentrate diet induced autophagy in mammary gland tissue through the Ca2+/CaMKKβ-AMPK signaling pathway, leading to inflammatory injury in dairy cows. [Read the Full Post]

Thiomyristoyl ameliorates colitis by blocking the differentiation of Th17 cells and inhibiting SIRT2-induced metabolic reprogramming

28 | Jul 24 2023

The study suggests that treatment with TM, a compound that targets SIRT2, reduces the progression of ulcerative colitis by inhibiting Th17 cell differentiation, promoting LDHA acetylation, and modulating inflammatory cytokines. [Read the Full Post]

A case of nocardiosis in a patient with ulcerative colitis on chronic corticosteroids, infliximab, and upadacitinib

98 | Jul 21 2023

Immunosuppressed patients, particularly those with ulcerative colitis, are at an increased risk of unmasking obscure infections, necessitating early detection and treatment to mitigate the associated morbidity and mortality. [Read the Full Post]

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis

34 | Jul 21 2023

Upadacitinib demonstrated higher therapeutic efficacy in reducing skin rashes in the lower limbs compared to the trunk and head and neck in patients with moderate-to-severe atopic dermatitis. [Read the Full Post]

Treatment satisfaction with molidustat in CKD-related anemia in non-dialysis patients: a post-hoc analysis of two clinical trials

33 | Jul 20 2023

The post-hoc analysis suggests that molidustat may offer improved treatment satisfaction and convenience compared to darbepoetin alfa for patients with non-dialysis chronic kidney disease and renal anemia. [Read the Full Post]

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

25 | Jul 20 2023

In conclusion, roxadustat demonstrated the highest efficacy in increasing hemoglobin levels but was associated with an increased risk of hypertension and thrombosis, while molidustat and ESAs may be preferable options for patients at risk of hypertension and thrombosis. [Read the Full Post]

Extracellular Release of Citrullinated Vimentin Directly Acts on Osteoclasts to Promote Bone Resorption in a Mouse Model of Periodontitis

46 | Jul 20 2023

The release of citrullinated vimentin (CV) promotes osteoclastogenesis and bone resorption in periodontitis, suggesting a potential shared pathogenesis with rheumatoid arthritis. [Read the Full Post]

TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma

61 | Jul 18 2023

The proposed therapeutic strategy in lymphoma combines PRMT5 inhibition with either MSI2 or BCL-2 inhibition, leveraging the synergistic effects observed to potentially enhance therapeutic efficacy. [Read the Full Post]

Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis

29 | Jul 18 2023

The study reveals that histidine decarboxylase deficiency in mice leads to disorderly recruitment of neutrophils, enhanced migration and ROS/NETs production, promoting cardiac damage, but treatment with histamine or PRMT1 inhibitors attenuates these effects, suggesting potential therapeutic strategies for cardiovascular disease. [Read the Full Post]

Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions

28 | Jul 16 2023

FLT3 inhibitors have improved clinical outcomes for acute myeloid leukemia patients with FLT3 mutations, but the emergence of resistance and the need for novel therapeutic strategies remain ongoing challenges. [Read the Full Post]

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase

0 | Jul 16 2023

The chromatin kinase VRK1 plays a crucial role in regulating the epigenetic patterns of histone H3 acetylation and methylation, thereby influencing chromatin organization and associated nuclear functions. [Read the Full Post]

Regulation, genomics, and clinical characteristics of cuproptosis regulators in pan-cancer

54 | Jul 16 2023

This study comprehensively elucidated the expression, prognostic significance, biological functions, genomic characteristics, immune microenvironment interactions, and drug sensitivity of cuproptosis regulators in pan-cancer, providing valuable insights into their potential role in cancer biology. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

0 | Jul 15 2023

The study found that intravenous administration of histone deacetylase inhibitors (HDACIs) was more effective than intraperitoneal administration, and both nonselective and isoform-specific HDACIs showed similar effects in improving survival and reducing histopathological damage, apoptosis, and inflammation in rats with hemorrhagic shock. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

82 | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

Simultaneous Inhibition of Histone Deacetylases and RNA Synthesis Enables Totipotency Reprogramming in Pig SCNT Embryos

36 | Jul 14 2023

In this study, the combined inhibition of histone deacetylases and RNA synthesis in swine SCNT embryos improved their developmental outcomes and increased the efficiency of the genome-editing + SCNT platform. [Read the Full Post]

PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis

29 | Jul 11 2023

PIM2 promotes the development of endometriosis through its role in enhancing glycolysis and fibrosis, suggesting it as a potential therapeutic target for the disease. [Read the Full Post]

In silico enhancer mining reveals SNS-032 and EHMT2 inhibitors as therapeutic candidates in high-grade serous ovarian cancer

78 | Jul 11 2023

This study utilized epigenomic profiling and a computational pipeline to identify potential therapeutic candidates and enhance stratification for ovarian cancer, with a focus on high-grade serous carcinoma. [Read the Full Post]

PIM Kinases in Multiple Myeloma

54 | Jul 10 2023

PIM kinase inhibitors show promise as a potential treatment for multiple myeloma, and their combination with other targeted agents, including immunomodulatory drugs, holds great potential for improving patient outcomes. [Read the Full Post]

PIM Kinase as an Executional Target in Cancer

104 | Jul 10 2023

PIM kinases, including PIM1, PIM2, and PIM3, are oncogenes that promote cell survival and cell cycle progression in various cancers, and the development of PIM kinase inhibitors shows promise in targeting these pathways for the treatment of human cancer. [Read the Full Post]

Formaldehyde exacerbates asthma in mice through the potentiation of HIF-1α-mediated pro-inflammatory responses in pulmonary macrophages

29 | Jul 08 2023

The study revealed that formaldehyde exposure exacerbates asthma by enhancing HIF-1α-mediated inflammatory responses in macrophages, indicating the potential universal role of formaldehyde-induced macrophage metabolic and functional alterations in inflammatory or allergic diseases. [Read the Full Post]

Exploring Synthetic Strategies for 1H-Indazoles and Their N-Oxides: Electrochemical Synthesis of 1H-Indazole N-Oxides and Their Divergent C-H Functionalizations

76 | Jul 08 2023

The research study describes a versatile electrochemical strategy for the selective synthesis of 1H-indazole N-oxides and their subsequent C-H functionalization, demonstrating its potential for the synthesis of diverse pharmaceutical molecules. [Read the Full Post]

Pelabresib (CPI-0610): An Exciting Novel Drug for the Treatment of Myelofibrosis

73 | Jul 02 2023

Pelabresib (CPI-0610), an investigational BET inhibitor, shows promising potential as a novel treatment approach for myelofibrosis, based on preclinical and clinical data demonstrating its ability to target key oncogenic signaling pathways and provide favorable responses in symptom control and disease-related parameters. [Read the Full Post]

A Phase I Study of Pelabresib (CPI-0610), a Small-Molecule Inhibitor of BET Proteins, in Patients with Relapsed or Refractory Lymphoma

14 | Jul 02 2023

The first-in-human phase I study of pelabresib demonstrated its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity, establishing a maximum tolerated dose of 225 mg once daily and supporting its potential as a therapeutic agent for relapsed/refractory lymphomas. [Read the Full Post]

Itacitinib Population Pharmacokinetics and Exposure-Response in Patients With Acute Graft-Versus-Host Disease

50 | Jul 01 2023

This article presents a population pharmacokinetic analysis and exposure-response assessment of itacitinib for the treatment of acute graft-versus-host disease, revealing significant predictors of treatment response and recommending dose reductions when co-administered with strong CYP3A inhibitors. [Read the Full Post]

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

42 | Jul 01 2023

PRMT6, an overexpressed arginine methyltransferase in glioma/GBM, promotes cell proliferation and progression by destabilizing CDKN1B through CDC20-mediated degradation, suggesting potential therapeutic targeting of the PRMT6-CDC20-CDKN1B axis in GBM. [Read the Full Post]

Downregulation of BASP1 promotes temozolomide resistance in gliomas via epigenetic activation of the FBXO32/NF-κB/MGMT axis

29 | Jul 01 2023

Downregulation of BASP1 in gliomas leads to enhanced resistance to TMZ therapy through activation of the FBXO32/NF-κB/MGMT axis via epigenetic modifications mediated by the WDR5/MLL complex, suggesting a potential therapeutic target for combating TMZ-resistant gliomas. [Read the Full Post]

GSK484, an inhibitor of peptidyl arginine deiminase 4, increases the radiosensitivity of colorectal cancer and inhibits neutrophil extracellular traps

44 | Jun 30 2023

The study demonstrates that the PAD4 inhibitor GSK484 enhances the radiosensitivity of colorectal cancer, induces cell death, and inhibits neutrophil extracellular trap (NET) formation, suggesting its potential as a therapeutic agent for improving treatment outcomes in CRC. [Read the Full Post]

The role of EZH2 as a potential therapeutic target in retinoblastoma

93 | Jun 30 2023

The study reveals that the high expression of EZH2 in retinoblastoma tissues is associated with poor overall survival, and inhibiting EZH2 with UNC1999 shows promising results in suppressing RB cell proliferation, metastasis, and tumor glycolysis, making it a potential target for anti-RB treatment. [Read the Full Post]

Resistance to Pyrrolobenzodiazepine Dimers Is Associated with SLFN11 Downregulation and Can Be Reversed through Inhibition of ATR

64 | Jun 30 2023

This study identified downregulation of Schlafen family member 11 (SLFN11) and its association with PBD resistance in cancer cells, highlighting the potential of targeting SLFN11 and combining ATR inhibitors to overcome resistance to PBD-conjugated ADCs. [Read the Full Post]

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

41 | Jun 29 2023

This retrospective study of 68 premature infants found no significant difference between male and female mixed-sex multiple gestation infants in terms of the most severe stage of retinopathy of prematurity (ROP) developed or the need for ROP treatment, but males received treatment at an earlier postmenstrual age (PMA) despite females having lower birthweight and slower growth velocity. [Read the Full Post]

Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction

47 | Jun 29 2023

Compound 189, identified through a high throughput compound screen, selectively inhibits the ATG12-ATG3 protein-protein interaction involved in autophagy, demonstrating potential as a therapeutic drug for autophagy-dependent tumors and inflammation. [Read the Full Post]

Sirtuin 1 activator alleviated lethal inflammatory injury via promotion of autophagic degradation of pyruvate kinase M2

74 | Jun 29 2023

The present study demonstrated that activation of SIRT1 through treatment with SRT2104 promotes autophagic degradation of pyruvate kinase M2 (PKM2), leading to reduced inflammation, improved organ function, and increased survival in lethal endotoxemia [Read the Full Post]

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase

56 | Jun 29 2023

The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation, particularly at lysines 4, 9, and 27, and is essential for coordinating chromatin organization and nuclear functions. [Read the Full Post]

LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials

0 | Jun 29 2023

This review summarizes the structure and functions of LSD1, its role in cancer and non-cancer diseases, and the potential of covalent and non-covalent LSD1 inhibitors, including those in clinical trials, as potent and selective anticancer agents. [Read the Full Post]

New therapy for pancreatic cancer based on extracellular vesicles

110 | Jun 25 2023

The study demonstrates that loading chemotherapeutic drugs into small extracellular vesicles derived from the RWP-1 cell line using the direct incubation method holds promise as an efficient drug delivery system for pancreatic ductal adenocarcinoma, with potential for further preclinical investigation and combination with a PRMT5 inhibitor in clinical trials. [Read the Full Post]

PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3 by stabilizing oncoprotein PML-RARα

57 | Jun 25 2023

The study demonstrates that PRMT5 is highly expressed in APL patients and its inhibition, either alone or in combination with As2O3, shows promising therapeutic potential by promoting the degradation of the oncogenic PML-RARα protein and inhibiting APL cell growth, differentiation, and survival. [Read the Full Post]

JAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL

0 | Jun 22 2023

The combination of a LSD1 inhibitor with a JAK/STAT pathway inhibitor or a BCL2 inhibitor reverses resistance and efficiently inhibits the growth of ETP-ALL cells, suggesting a potential novel combination therapy for ETP-ALL patients. [Read the Full Post]

FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

100 | Jun 20 2023

Interference with FOXK1 in nasopharyngeal carcinoma cells through the JAK/STAT3 pathway regulates EMT, enhances radiosensitivity, and inhibits tumor progression [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

0 | Jun 20 2023

JAK inhibitors have shown promise in treating rheumatoid arthritis by selectively modulating immune and inflammatory pathways, although their in vivo selectivity and long-term safety profile still require further investigation. [Read the Full Post]

Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia

107 | Jun 19 2023

The study demonstrates that sustained treatment with the JAK/TYK2 inhibitor cerdulatinib leads to JAK1 overexpression and enhanced JAK/STAT signaling in TYK2-rearranged ALL cells, but withdrawal of the drug reverses these effects, while histone deacetylase inhibitor (HDACi) therapies show efficacy against cerdulatinib-resistant cells, offering a potential alternative treatment approach for TYK2-rearranged B-ALL patients who have developed resistance to JAKi. [Read the Full Post]

NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer

22 | Jun 19 2023

The study reveals that the RNA modification ac4C, mediated by NAT10, promotes cisplatin chemoresistance in bladder cancer by enhancing DNA damage repair through stabilization of AHNAK mRNA, and targeting NAT10 could be a potential therapeutic approach to overcome cisplatin resistance in bladder cancer. [Read the Full Post]

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study

66 | Jun 18 2023

The FilgoColitis study is a prospective observational study evaluating the long-term effectiveness of filgotinib in patients with active ulcerative colitis, focusing on patient-reported outcomes and incorporating the use of innovative wearables to collect physical activity data. [Read the Full Post]

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

35 | Jun 18 2023

This interventional clinical trial aims to compare the effectiveness of filgotinib monotherapy to tocilizumab monotherapy in rheumatoid arthritis patients with an inadequate response to methotrexate, utilizing clinical disease activity indices, musculoskeletal ultrasound, and serum biomarkers as evaluation parameters. [Read the Full Post]

HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma

88 | Jun 18 2023

The study reveals that the HDAC4/LHPP signaling axis promotes the proliferation and metastasis of nasopharyngeal carcinoma through upregulation of TYK2-STAT1 phosphorylation activation, providing new insights and potential intervention targets for NPC metastasis. [Read the Full Post]

Targeting the undruggable: menin inhibitors ante portas

44 | Jun 18 2023

The menin-MLL axis inhibitors show promise as targeted therapies for acute myeloid leukemias with MLL rearrangements and NPM1 mutations, with early clinical data demonstrating favorable response rates and potential for improved outcomes. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

43 | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer

79 | Jun 17 2023

The study demonstrates the potential of hyaluronic acid-decorated metal-organic frameworks delivering the JMJD3 demethylase inhibitor GSK-J1 (HA@MOF@GSK-J1) as an effective and targeted strategy for treating carboplatin-resistant ovarian cancer. [Read the Full Post]

Astrocytic c-Jun N-terminal kinase-histone deacetylase-2 cascade contributes to glutamate transporter-1 decrease and mechanical allodynia following peripheral nerve injury in rats

26 | Jun 17 2023

The decrease of glutamate transporter-1 (GLT-1) and upregulation of histone deacetylase 2 (HDAC2) in spinal astrocytes, mediated by the JNK-HDAC2 cascade and neuroimmune activation, contribute to enhanced excitatory transmission and the development of persistent pain following peripheral nerve injury. [Read the Full Post]

Porcine Deltacoronavirus Infection Cleaves HDAC2 to Attenuate Its Antiviral Activity

55 | Jun 17 2023

The study revealed that porcine deltacoronavirus (PDCoV) infection inhibits cellular histone deacetylase 2 (HDAC2) activity through cleavage by the viral nonstructural protein 5 (nsp5), highlighting a common strategy employed by mammalian coronaviruses to counteract the antiviral role of HDAC2 and providing potential targets for the development of antiviral drugs. [Read the Full Post]

Inhibition of histone methyltransferase SETD8 represses DNA virus replication

36 | Jun 16 2023

UNC0379, an inhibitor of histone H4K20 methyltransferase SETD8, shows promise as an effective inhibitor of multiple DNA viruses by enhancing the expression of anti-viral genes and repressing viral replication, potentially offering a new strategy for the treatment of DNA virus-related diseases. [Read the Full Post]

Episodes of Early Pleistocene West Antarctic Ice Sheet Retreat Recorded by Iceberg Alley Sediments

31 | Jun 16 2023

This study in the Scotia Sea provides evidence of past episodes of West Antarctic Ice Sheet instability and suggests that intense IBRD deposition, likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s), occurred during a warm climate phase approximately 1.2 million years ago. [Read the Full Post]

Comparison of pharmacological inhibitors of lysine-specific demethylase 1 in glioblastoma stem cells reveals inhibitor-specific efficacy profiles

80 | Jun 16 2023

This study demonstrates the cytotoxic effects of LSD1 inhibitors in patient-derived glioblastoma models and identifies potential resistance-associated genes, providing valuable insights for the development of future combination therapies. [Read the Full Post]

SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis

51 | Jun 16 2023

This study demonstrates that inhibiting SIRT2 during BCG vaccination enhances the immune response, particularly the generation of stem cell memory T cells, and suggests SIRT2 inhibitors as potential immunoprophylaxis against tuberculosis. [Read the Full Post]

The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression

107 | Jun 15 2023

The study revealed that the anti-tumor effect of the HDAC inhibitor domatinostat on Merkel cell carcinoma cells is mediated through the suppression of HES1, allowing for the induction of IFNα and subsequent apoptosis. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

55 | Jun 15 2023

The study found that intravenous administration of nonselective and isoform-specific HDACIs, including MS-275, LMK-235, tubastatin A, and TSA, was superior to intraperitoneal administration in improving survival rates and reducing histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels in rats with hemorrhagic shock. [Read the Full Post]

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

31 | Jun 13 2023

The study demonstrates that the inhibition of ERK5, regulated by miR-143, holds promise as a potential therapeutic target for the treatment of clear cell renal cell carcinoma (ccRCC). [Read the Full Post]

Dimethyloxalylglycine Attenuates Steroid-Associated Endothelial Progenitor Cell Impairment and Osteonecrosis of the Femoral Head by Regulating the HIF-1α Signaling Pathway

34 | Jun 11 2023

Targeting hypoxia-inducible factor-1α (HIF-1α) in endothelial progenitor cells (EPCs) may offer a novel therapeutic approach for the treatment of steroid-associated osteonecrosis of the femoral head (SONFH) by alleviating glucocorticoid-induced endothelial impairment, promoting angiogenesis and osteogenesis, and enhancing the homing of EPCs to the injured endothelium. [Read the Full Post]

The Class IIA Histone Deacetylase (HDAC) Inhibitor TMP269 Downregulates Ribosomal Proteins and Has Anti-Proliferative and Pro-Apoptotic Effects on AML Cells

36 | Jun 04 2023

The study found that HDAC genes are overexpressed in AML patients and cell lines, and that TMP269, a class IIA HDAC inhibitor, has anti-leukemic activity when combined with venetoclax and may be a potential therapeutic drug for AML. [Read the Full Post]

From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors

100 | Jun 04 2023

The passage describes the discovery of a potent BET inhibitor called 1q (SJ1461) through a CLICK chemistry-based approach, which shows improved profiles compared to existing BET inhibitors and has promising potential for further development as a cancer therapy. [Read the Full Post]

NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors

114 | Jun 03 2023

This study highlights the need for cautious evaluation and dosage optimization of inhibitors targeting respiratory complex I in cancer treatment. [Read the Full Post]

Dual mechanism: Epigenetic inhibitor apabetalone reduces SARS-CoV-2 Delta and Omicron variant spike binding and attenuates SARS-CoV-2 RNA induced inflammation

5 | Jun 02 2023

The passage discusses the potential use of apabetalone, an inhibitor of epigenetic regulators, for the treatment of COVID-19 and post-COVID syndrome by reducing ACE2 expression and countering pro-inflammatory factors regardless of the SARS-CoV-2 variant. [Read the Full Post]

Epigenetics in Obesity and Diabetes Mellitus: New Insights

27 | Jun 02 2023

Obesity-related diseases such as type 2 diabetes are associated with epigenetic modifications that can lead to stable changes in gene expression, and targeting these modifications with drugs like apabetalone holds promise as a potential treatment strategy. [Read the Full Post]

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids

25 | Jun 02 2023

PARP1 promotes HMGB1 secretion in intestinal inflammation, and inhibiting PARP1 could be a novel approach to manage inflammatory bowel diseases. [Read the Full Post]

Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-β signaling

38 | Jun 01 2023

This study suggests that USP2 is a major regulator of the TGF-β signaling pathway in glioblastoma, and its loss leads to poor prognosis in patients, while DNMT3A inhibitor SGI-1027 could be a potential treatment by inducing USP2 expression and suppressing TGF-β signaling. [Read the Full Post]

Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats

24 | Jun 01 2023

The study suggests that KDM4D, a specific demethylase of residue H3K9, plays a key role in modulating the expression of AgRP, a key neuropeptide that regulates hunger response, and may offer a target to develop new treatments for obesity. [Read the Full Post]

Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways

64 | May 31 2023

The study shows that pharmacologic inhibition of PARP5 unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs. [Read the Full Post]

Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation-driven hepatocarcinogenesis

65 | May 31 2023

The study shows that targeting YAP/TAZ is an effective treatment against hepatocellular carcinoma (HCC) with loss-of-function mutations of AXIN1. [Read the Full Post]

UPP1 Promotes Lung Adenocarcinoma Progression through Epigenetic Regulation of Glycolysis

28 | May 31 2023

This study characterized the function and underlying mechanisms of Uridine phosphorylase 1 (UPP1) in mediating the progression of Lung Adenocarcinoma (LUAD) cells, confirming it as a novel oncogene and a potential therapeutic target for LUAD. [Read the Full Post]

Right Ventricular Dysfunction and Exercise Impairment in Patients with Heart Failure, Insulin Resistance, and Diabetes Mellitus: Insights from the T.O.S.CA. Registry (Cardiovascular Diabetology 2022)

26 | May 31 2023

The study findings suggest that insulin resistance and type 2 diabetes mellitus have a negative impact on right ventricular function, exercise tolerance, and cardiovascular outcomes, highlighting the need for early detection and management of these conditions. [Read the Full Post]

G9a/GLP Targeting Ameliorates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

27 | May 30 2023

This study suggests that inhibiting the histone methyltransferase G9a and its partner protein GLP may be a new therapeutic approach in pulmonary arterial hypertension. [Read the Full Post]

Inhibition of BRD4 enhanced the tumor suppression effect of dasatinib in gastric cancer

7 | May 29 2023

The study suggests that targeting BRD4 in gastric cancer may improve patient prognosis and increase the sensitivity of chemotherapy drugs such as dasatinib. [Read the Full Post]

Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

35 | May 29 2023

The study found that exercise can reduce ventilator-induced lung injury by inhibiting PKCɑ and NLRP3 activation. [Read the Full Post]

Temperature sensing by the calcium-sensing receptor

48 | May 29 2023

The study suggests that CaSRs, a type of GPCR, may contribute to temperature sensing through a mechanism dependent on repetitive phosphorylation and dephosphorylation. [Read the Full Post]

Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells

95 | May 26 2023

The study investigates the potential of using an EZH2 inhibitor, HKMTI-1-005, to improve the response of non-APL AML cells to ATRA-based therapy by inducing differentiation and upregulating the expression of differentiation pathway genes. [Read the Full Post]

Alteration of the tumor microenvironment by pharmacological inhibition of EZH2 in hepatocellular carcinoma

30 | May 26 2023

The study found that EZH2 inhibition with UNC1999 impaired HCC tumor growth but also altered the TME by decreasing interferon-γ+ CD8+ T cells and regulatory T cells and increasing myeloid-derived suppressor cells, and combination therapy with agents that reduce MDSCs may represent a potential novel therapeutic strategy for HCC. [Read the Full Post]

A patent review of EZH2 inhibitors from 2017 and beyond

74 | May 23 2023

EZH2 inhibitors are a promising class of drugs for the treatment of various diseases, particularly cancers, but further research is needed to optimize their efficacy and safety. [Read the Full Post]

FZD7, Regulated by Non-CpG Methylation, Plays an Important Role in Immature Porcine Sertoli Cell Proliferation

28 | May 22 2023

This study explores the regulatory roles of non-CpG methylation in testicular development, identifying several hub genes such as FZD7, which is found to be important in linking the proliferation and apoptosis of Sertoli cells. [Read the Full Post]

The Protective Effect of Zebularine, an Inhibitor of DNA Methyltransferase, on Renal Tubulointerstitial Inflammation and Fibrosis

24 | May 22 2023

Inhibiting DNA methylation can restore the balance between pro-inflammatory and anti-inflammatory pathways, alleviate renal inflammation and fibrosis, and highlight DNA methyltransferases as potential therapeutic targets for treating chronic kidney disease. [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

60 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

JMJD3 Promotes Myeloid Fibroblast Activation and Macrophage Polarization in Kidney Fibrosis

82 | May 20 2023

This study demonstrates that JMJD3 plays a crucial role in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development, making it a potential therapeutic target for chronic kidney disease. [Read the Full Post]

DOT1L promotes cell proliferation and invasion by epigenetically regulating STAT5B in renal cell carcinoma

24 | May 20 2023

Targeting DOT1L may be a potential therapeutic intervention for renal cell carcinoma as it promotes RCC progression by epigenetically promoting STAT5B transcription in a histone methyltransferase-dependent manner. [Read the Full Post]

The Effect of Direct and Indirect EZH2 Inhibition in Rhabdomyosarcoma Cell Lines

48 | May 17 2023

The study found that direct and indirect inhibition of EZH2 affect cellular functions differently, and the alveolar cell line RH30 is more sensitive to epigenetic intervention than the embryonal cell line RD, suggesting EZH2 as a potential therapeutic target in RMS. [Read the Full Post]

LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials

38 | May 13 2023

LSD1 is an epigenetic enzyme overexpressed in many types of cancers, and its inhibitors have emerged as a promising therapeutic strategy for selectively targeting cancer cells while sparing normal cells. [Read the Full Post]

Recent advances of LSD1/KDM1A inhibitors for disease therapy

24 | May 13 2023

The review highlights recent advances and challenges in LSD1-targeted drug discovery for the treatment of various diseases, including hematologic malignancies. [Read the Full Post]

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

36 | May 13 2023

The study found that LRRK1 is activated by PKC-dependent phosphorylation of a cluster of conserved residues within a region of the CORB domain, which promotes interaction and stabilization of the αC-helix on the kinase domain, revealing a novel activation mechanism. [Read the Full Post]

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma

64 | May 13 2023

The phase Ib study found that the combination of sotrastaurin and alpelisib was tolerable but showed limited clinical activity in patients with metastatic uveal melanoma or GNAQ/11 mutant cutaneous melanoma. [Read the Full Post]

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model

27 | May 11 2023

Bobcat339, a synthetic small molecule that binds to the catalytic pockets of TET proteins, shows potential as a therapeutic for anorexia nervosa and stress-related disorders by inducing TET3 protein degradation and stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner. [Read the Full Post]

Inactivation of KDM5A suppresses growth and enhances chemosensitivity in liver cancer by modulating ROCK1/PTEN/AKT pathway

25 | May 07 2023

Targeting the inactivation of KDM5A can enhance the chemosensitivity of liver cancer cells to CDDP through modulating the ROCK1/PTEN/AKT signaling pathway. [Read the Full Post]

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations

90 | May 06 2023

The study identified multiple independent predictors of failure of middle meningeal artery embolization treatment for chronic subdural hematoma, with small diameter being the only factor independently associated with both clinical and radiographic failures. [Read the Full Post]

Molecular Design of 68Ga- and 89Zr-Labeled Anticalin Radioligands for PET-Imaging of PSMA-Positive Tumors

62 | May 05 2023

The study demonstrates the potential of Anticalin proteins as radioligands for PET-imaging of xenograft tumors in mice, with the use of PASylation technology to tailor their plasma half-life and the cyclic radiochelator FsC being superior to Dfo for 89Zr-ImmunoPET-imaging. [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

87 | Apr 29 2023

JAK inhibitors represent a promising class of drugs for the treatment of rheumatoid arthritis, with varying degrees of selectivity for different JAK isoforms, and precision medicine approaches may enhance their effectiveness in the future. [Read the Full Post]

Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress

58 | Apr 22 2023

The study found that ZEA induces dysfunction of MAM in piglet SCs via the ERS pathway, and pretreatment with the ERS inhibitor 4-PBA can reduce ZEA-induced toxicity and regulate the expression of key proteins involved in MAM function. [Read the Full Post]

Adequacy of energy and macronutrients intake in differently active slovenian adolescents

132 | Apr 21 2023

The study found that a significant proportion of Slovenian adolescents are not meeting national recommendations for energy and macronutrient intake, and there were differences in energy/macronutrient intake between boys of different physical activity levels, highlighting the need for interventions to encourage healthy eating and physical activity behaviors. [Read the Full Post]

Perinatal Stressors as a Factor in Impairments to Nervous System Development and Functions: Review of In Vivo Models

82 | Apr 21 2023

This review evaluates different models of perinatal pathology and their relationship with psychoemotional stressors in understanding the impact of stress on the developing brain and behavior. [Read the Full Post]

Clinical benefit of MAO-B and COMT inhibition in Parkinson's disease: practical considerations

78 | Apr 16 2023

MAO-B and COMT inhibitors are important strategies for managing motor fluctuations in Parkinson's disease patients, with several drugs available on the market targeting these enzymes, and ongoing studies exploring new formulations and combinations of these inhibitors. [Read the Full Post]

Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation

69 | Apr 14 2023

This case report suggests that romidepsin may be a safe and effective treatment option for patients with relapsed or refractory PTCL-TFH after allogeneic HCT. [Read the Full Post]

Nicotinamide riboside supplementation is not associated with altered methylation homeostasis in Parkinson's disease

48 | Apr 13 2023

The study found that short-term therapy with high-dose nicotinamide riboside (NR) for up to 30 days had no negative impact on DNA methylation homeostasis in individuals with Parkinson's disease. [Read the Full Post]

O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells

33 | Apr 12 2023

The study investigated the involvement of O-GlcNAc modification in the inflammatory signaling pathway of endothelial cells under LPS stimulation and found that increasing OGT expression could inhibit the activation of the inflammatory signal pathway and reduce inflammatory cytokine expression, and that the PI3K/Akt pathway is involved in regulating O-GlcNAc modification in response to LPS stimulation. [Read the Full Post]

Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection

93 | Apr 09 2023

Recent research shows that Omicron but not Delta induces a strong interferon response in primary human cells, protects cells from super-infection with influenza A viruses, and the response is mediated via MDA5 recognition of double-stranded RNA and involves the production of biologically active type I (α/β) and III (λ) interferons. [Read the Full Post]

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy

66 | Apr 09 2023

Oral baricitinib combined with NB-UVB phototherapy has shown to be a successful treatment option for refractory vitiligo by blocking the JAK-STAT pathway and stimulating melanocyte production. [Read the Full Post]

Prelimbic Cortical Stimulation with L-methionine Enhances Cognition through Hippocampal DNA Methylation and Neuroplasticity Mechanisms

26 | Apr 07 2023

The study suggests that targeting hippocampal DNA methyltransferase (DNMT) through prelimbic cortical deep brain stimulation (PrL DBS) and L-methionine (MET) co-administration may enhance memory and serve as a potential therapeutic approach for treating dementia. [Read the Full Post]

Distinct Protein Kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes

30 | Apr 06 2023

The study found that distinct PKC isoforms are responsible for the preferential appearance of nestin(+)- or nestin(-)-NNVMs that re-enter the cell cycle in the presence of SB203580. [Read the Full Post]

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy

71 | Apr 04 2023

This study demonstrates the pathological role of non-canonical NLRC4 inflammasomes in glioma and proposes therapeutic strategies based on modulating the inflammatory tumor microenvironment. [Read the Full Post]

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors

0 | Apr 04 2023

Sub-type selective Aurora kinase inhibitors targeting specific residues unique to either Aurora A or B may have advantages over pan-selective inhibitors and could be useful in the treatment of cancer. [Read the Full Post]

CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells

54 | Apr 03 2023

CUDC907, a dual HDAC/PI3K inhibitor, selectively reduces the viability of human merlin deficient Schwann cells (MD-SCs), promotes cell cycle arrest and caspase-3/7 activation, decreases levels of pAKT and YAP, and shows potential as a therapeutic option for Neurofibromatosis Type 2 (NF2). [Read the Full Post]

Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia

51 | Apr 03 2023

The study found that the combination of CUDC-907 and venetoclax induces metabolic and transcriptomic reprogramming and suppresses oxidative phosphorylation in AML cells, providing a promising therapeutic approach for AML. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

110 | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

126 | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

Transporter‑mediated drug‑drug interactions involving poly (ADP‑ribose) polymerase inhibitors (Review)

100 | Apr 01 2023

Transporter-mediated drug-drug interactions should be considered when co-administering PARP inhibitors with other therapeutic agents to avoid potential toxicity or suboptimal efficacy. [Read the Full Post]

Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells

18 | Mar 31 2023

Inhibition of Aurora kinases combined with blockade of the Wnt/beta-catenin pathway may provide a promising combinatorial approach for targeting ACC tumors. [Read the Full Post]

Mechanistic insight into the protective effects of fisetin against arsenic-induced reproductive toxicity in male rats

38 | Mar 22 2023

The study found that fisetin treatment was effective in mitigating the reproductive damage caused by arsenic exposure in male albino rats, indicating its potential as a therapeutic candidate against arsenic-generated male reproductive toxicity. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

139 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

118 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

Mechanisms of paeoniaceae action as an antidepressant

44 | Mar 22 2023

Paeoniflorin (PF) has been shown to have multiple mechanisms through which it exerts its antidepressant effects, including increasing the levels of monoamine neurotransmitters, inhibiting the HPA axis, promoting neuroprotection, enhancing neurogenesis in the hippocampus, and elevating levels of BDNF. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

87 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

Selective inhibition of HDAC6 promotes bladder cancer radiosensitization and mitigates the radiation-induced CXCL1 signalling

67 | Mar 20 2023

This study found that selective inhibition of histone deacetylase 6 (HDAC6) can enhance the radiosensitivity of bladder cancer cells and suppress radiation-induced oncogenic signaling, suggesting its potential as a therapeutic strategy in combination with radiation therapy. [Read the Full Post]

Delayed aortic regurgitation after TEVAR procedure: a case report

75 | Mar 20 2023

This case report underscores the importance of careful attention and technique when performing catheter-related procedures around the aortic valve to prevent delayed aortic insufficiency. [Read the Full Post]

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

115 | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

PARP-1 inhibitor-AG14361 suppresses acute allograft rejection via stabilizing CD4+FoxP3+ regulatory T cells

34 | Mar 16 2023

The PARP-1 inhibitor AG14361 may be a promising agent to attenuate acute allograft rejection by maintaining the number and function of Treg cells in allografts. [Read the Full Post]

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

83 | Mar 13 2023

The study suggests that co-inhibition of HDAC6 and HDAC8 through selective inhibitors could be a novel therapeutic approach for ovarian cancer patients with wild-type p53. [Read the Full Post]

Effects of supplementing organic- and inorganic-based selenium with vitamin E on intestinal histomorphology, caecal bacterial proliferation, and short-chain fatty acid profile in layer hens

103 | Mar 12 2023

Organic selenium supplementation, particularly bacterial organic selenium, enhances intestinal histomorphology, increases beneficial caecal bacterial proliferation, and increases butyric acid content in layer chickens. [Read the Full Post]

Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy

54 | Mar 10 2023

Kaempferol binds to NOX4 and inhibits NOX4-mediated autophagy, providing an effective therapeutic strategy for treating asthma by decreasing NOX4 expression and improving airway inflammation and remodeling. [Read the Full Post]

Effect of hybrid compounds of stilbene and pentadienone on inhibition of tubulin polymerization

93 | Mar 09 2023

The study designed and synthesized hybrid compounds with excellent anticancer properties that inhibit tubulin polymerization and induce cell cycle arrest in MDA-MB-231 human breast cancer cells. [Read the Full Post]

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

72 | Mar 08 2023

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy with diverse clinical manifestations and poor prognosis that requires a combination of clinical, morphological and immunophenotypic features for diagnosis and individualized treatment. [Read the Full Post]

Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy

95 | Mar 07 2023

The phase I/II trial showed that cusatuzumab plus azacitidine was generally well-tolerated and showed preliminary efficacy in newly diagnosed AML patients ineligible for intensive chemotherapy, with ongoing investigation into the combination with venetoclax and azacitidine. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

134 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

161 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors

66 | Feb 23 2023

This review article focuses on the role of STAT3 in the development and progression of breast cancer, and the potential of phytochemicals, synthetic molecules, and biologicals to inhibit JAK-STAT and STAT3, as a promising approach in the development of better therapeutics against breast cancer. [Read the Full Post]

The novel histone deacetylase inhibitor pracinostat suppresses the malignant phenotype in human glioma

33 | Feb 23 2023

Pracinostat is a promising novel therapy for human glioma, as it inhibited proliferation, induced apoptosis, and reduced migration and invasion, while also affecting the PI3K/Akt and STAT3 pathways. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

95 | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

208 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

118 | Feb 18 2023

Tfr2 deletion results in increased joint swelling and bone erosion in a K/BxN serum-transfer arthritis model, which may be due to Tfr2's role in suppressing pro-inflammatory M1-like polarization in macrophages. [Read the Full Post]

Camptothecin analogs in malignant gliomas: comparative analysis and characterization

47 | Feb 14 2023

The authors compared and characterized several new classes of camptothecin analogs and found that 10,11-methylenedioxy class consistently demonstrated the greatest cytotoxicity and hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. [Read the Full Post]

Population pharmacokinetic analysis of TQ-B3203 following intravenous administration of TQ-B3203 liposome injection in Chinese patients with advanced solid tumors

174 | Feb 14 2023

A population pharmacokinetic model was successfully developed for TQ-B3203, a novel topoisomerase I inhibitor, in Chinese patients with advanced solid tumors and showed that body mass index, lean body weight, and direct bilirubin were significant covariates that affected TQ-B3203 pharmacokinetics. [Read the Full Post]

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles

57 | Feb 13 2023

Aurora kinase inhibitors were identified through a high-throughput cell-based assay as potent inhibitors of herpes simplex virus 1 (HSV-1) gene expression and replication, as well as reducing replication of other RNA and DNA viruses including vaccinia virus and mouse hepatitis virus, demonstrating that aurora kinases play a pivotal role in the life cycles of diverse viruses. [Read the Full Post]

Zearalenone and its metabolite exposure directs oestrogen metabolism towards potentially carcinogenic metabolites in human breast cancer MCF-7 cells

74 | Feb 11 2023

Mycoestrogens increase the production of CYP1B1-mediated oestrogen catechol metabolites, directing the biotransformation of E2 towards 4-OHE2, a crucial factor in oestrogen-induced tumour initiation. [Read the Full Post]

Synthesis and antiproliferative activity evaluation of B-norcholesterol-6-amide compounds

69 | Feb 10 2023

The study found that introducing chloroalkyl acyl groups into the 6-position of 6-amino-B-norcholesterol greatly enhanced the cytotoxicity of the resulting B-norcholesterol-6-amide compounds, with compound 20 having an IC50 value of 3.9 μM on HeLa cells. [Read the Full Post]

[Single-center study of different treatment for advanced or unresectable angiosarcoma patients]

125 | Feb 06 2023

This study found that doxorubicin-based and paclitaxel-based chemotherapy are the most common treatments for advanced angiosarcoma, and combined targeted therapy with anti-PD-1 immunotherapy showed potential efficacy in some patients with long duration of response and moderate adverse events. [Read the Full Post]

Decitabine enhances the tumoricidal potential of TRAIL via the epigenetic regulation of death receptor 4 in gastric cancer

83 | Feb 05 2023

Decitabine enhances the anti-tumor effect of TRAIL by upregulating DR4 expression through epigenetic modification, acting as a sensitizing agent, and providing a novel idea for gastric cancer treatment when used in combination. [Read the Full Post]

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

103 | Feb 05 2023

The study of combining decitabine and ipilimumab for AML/MDS showed that the clinical response to the combination therapy is primarily driven by decitabine-induced cytoreduction, but evidence of immune activation was only observed after ipilimumab exposure, and long-lasting responses require elimination of leukemic progenitor cells. [Read the Full Post]

Targeting aurora kinase B alleviates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury

31 | Jan 29 2023

Yu Shen et al. indicated that AURKB played a critical role in spinal microgliosis and neuropathic pain. [Read the Full Post]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

126 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

Identifying the role of transient receptor potential channels (TRPs) in kidney renal clear cell carcinoma and their potential therapeutic significances using genomic and transcriptome analyses

71 | Jan 15 2023

Jie Ren et al. provided useful insight that could aid and guide clinical practice and scientific research. [Read the Full Post]

Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma

55 | Jan 14 2023

Miaorong Xu et al. thought that a ten-cuproptosis-related lncRNA signature was constructed that provided promising insights into personalized prognosis and drug selection among COAD patients. [Read the Full Post]

Increased HRD score in cisplatin resistant penile cancer cells

55 | Jan 14 2023

Ria Winkelmann et al. found that UKF-PEC-1rCDDP2500 did not display sensitivity to PARP inhibitors. [Read the Full Post]

Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma

112 | Jan 13 2023

Filippo Spriano et al. identified combinations that could improve the response to BET inhibitors in lymphomas. [Read the Full Post]

Case report: olaparib use in metastatic lung adenocarcinoma with BRCA2 pathogenic variant

32 | Jan 10 2023

Jonathan Soon Jian Hao et al. highlighted the utility of next-generation sequencing in identifying gene mutations. [Read the Full Post]

Guhong Injection Alleviates Cerebral Ischemia-Reperfusion Injury via the PKC/HIF-1α Pathway in Rats

86 | Jan 08 2023

Li Yu et al. confirmed GHI could ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway. [Read the Full Post]

PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling

42 | Jan 08 2023

Jodie Hay et al. demonstrated that PKCβ expression facilitates leukemogenesis and identified that BCR-mediated signalling was a key driver of CLL development in the PKCα-KR model. [Read the Full Post]

Racial and Ethnic Differences in Internal Medicine Residency Assessments

103 | Jan 06 2023

Dowin Boatright et al. found that URiM and Asian internal medicine residents received lower ratings on performance assessments than their White peers during the first and second years of training. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

65 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

76 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

95 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Comparison of efficacy of roxadustat and erythropoietin for the treatment of renal anemia in patients with chronic kidney disease: a retrospective study

42 | Dec 21 2022

Chen Jin et al. thought that orally administered roxadustat improved hemoglobin levels more than rhEPO in patients with CKD and anemia. [Read the Full Post]

Preclinical Evaluation of an 18F-Labeled SW-100 Derivative for PET Imaging of Histone Deacetylase 6 in the Brain

24 | Dec 19 2022

Tetsuro Tago et al. suggested that [18F]2 was a potentially useful PET radioligand for brain HDAC6 imaging. [Read the Full Post]

Protein kinase C-β distinctly regulates blood-brain barrier-forming capacity of Brain Microvascular endothelial cells and outgrowth endothelial cells

38 | Dec 06 2022

Rais Reskiawan A Kadir et al. thought that targeting PKC-β signalling pathway in ischaemic settings required close attention while using OECs as cellular therapeutic. [Read the Full Post]

PKCβ Inhibition Promotes TXNIP Degradation to Ameliorate Pancreatic β-Cell Dysfunction

50 | Dec 05 2022

Shijun He et al. suggested that KCβ inhibitor was a promising agent for ameliorating β-cell dysfunction through TXNIP. [Read the Full Post]

DOT1L regulates MTDH-mediated angiogenesis in triple-negative breast cancer: intermediacy of NF-κB-HIF1α axis

33 | Dec 01 2022

Praveen Kumar Neeli et al. thought that the therapeutic disruption of the DOT1L-MTDH-NF-κB-HIF1α axis might have usefulness in the management of TNBC. [Read the Full Post]

JAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL

118 | Nov 28 2022

Aissa Benyoucef et al. revealed the novel involvement of ZEB2/LSD1 complexes in repressing the intrinsic apoptosis pathway by inhibiting the expression of several pro-apoptotic proteins such as BIM (BCL2L11) as a major driver for ETP-ALL survival. [Read the Full Post]

Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival

115 | Nov 27 2022

Naseema Gangat et al. suggested a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF. [Read the Full Post]

MPN-379 Matching-Adjusted Indirect Comparison (MAIC) of Pelabresib (CPI-0610) in Combination With Ruxolitinib vs. JAK Inhibitor Monotherapy in Patients With Intermediate or High-Risk Myelofibrosis

125 | Nov 27 2022

Vikas Gupta et al. suggested that MAIC-adjusted improvements observed in SVR35 and TSS50 at Week 24 with pelabresib and ruxolitinib vs. ruxolitinib, fedratinib, or momelotinib monotherapy were consistent with unadjusted comparisons. [Read the Full Post]

Hypoxia inducible factor 1α inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells

27 | Nov 22 2022

Masanobu Tsubaki et al. indicated that HIF-1α regulated BCR-ABL and Met expression and was involved in cell survival in CML cells. [Read the Full Post]

HO-1 promotes resistance to an EZH2 inhibitor through the pRB-E2F pathway: correlation with the progression of myelodysplastic syndrome into acute myeloid leukemia

0 | Nov 17 2022

Zhengchang He et al. thought that HO-1 could influence MDS resistance and progression to AML. [Read the Full Post]

Ricolinostat suppresses proliferation, promotes apoptosis, and enhances the antiproliferative activity of topoisomerase inhibitors in cervical cancer cells

55 | Nov 14 2022

Sumeet Kaur et al. found that ricolinostat suppressed proliferation by inducing G2/M phase arrest and promoted apoptosis in cervical cancer cells, indicating that ricolinostat might be a promising antitumor agent in cervical cancer. [Read the Full Post]

High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors

0 | Nov 09 2022

Tatjana Ullmann et al. found that I-BET151 and HDAC inhibitors simultaneously upregulated the mRNA expression of pro-inflammatory IL-1ß. [Read the Full Post]

Overexpression of bromodomain and extraterminal domain is associated with progression, metastasis and unfavorable outcome: highlighting prognostic and therapeutic value of BET protein family in gastric cancer

8 | Nov 08 2022

Shahrzad Soleymani Fard et al. provided insights into the prognostic role of BET family in GC and proposed BET inhibition as a therapeutic strategy for GC patients. [Read the Full Post]

Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection

45 | Nov 06 2022

Kendra R Vann et al. provided insight into molecular mechanisms that contributed to SARS-CoV-2 pathogenesis and shed light on a new strategy to block SARS-CoV-2 infection. [Read the Full Post]

AMPK-driven Macrophage Responses are Autophagy-dependent in Experimental Bronchopulmonary Dysplasia

41 | Nov 03 2022

Sourabh Soni et al. found that pharmacologic activation of AMPK by AICAR resulted in induction of autophagy and played a protective role. [Read the Full Post]

Acadesine alleviates acute pancreatitis-related lung injury by mediating the barrier protective function of pulmonary microvascular endothelial cells

30 | Nov 03 2022

Xiandong Zhu et al. found that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. [Read the Full Post]

HDAC inhibitor quisinostat prevents estrogen deficiency-induced bone loss by suppressing bone resorption and promoting bone formation in mice

49 | Nov 01 2022

Shengxuan Sun et al. provided the first preclinical evidence to support Qst as a potential therapeutic agent for PMOP prevention and treatment. [Read the Full Post]

Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma

42 | Nov 01 2022

Masaya Nakano et al. showed that p63 was not only a diagnostic marker of salivary gland neoplasia, but it also promoted the malignancy. [Read the Full Post]

Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer

104 | Oct 28 2022

Md Shahin Alam et al. validated that masitinib inhibited the mTOR signaling pathway and induced apoptotic cell death. [Read the Full Post]

Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia

62 | Oct 27 2022

Wenjun Wang et al. thought that a low expression level of SLC25A21 predicted an unfavourable prognosis in patients with AML. [Read the Full Post]

Expression patterns and therapeutic implications of histone deacetylase-1 across carcinomas: a comprehensive molecular docking and MD simulation study

69 | Oct 24 2022

Bader Alshehri signified that targeting HDAC1 was a promising therapeutic strategy, and exploring novel therapeutic agents through basic, translational design might lead to their ultimate use in cancer prevention. [Read the Full Post]

Clinical and immune correlate results from a phase 1b study of the histone deacetylase inhibitor mocetinostat with ipilimumab and nivolumab in unresectable stage III/IV melanoma

63 | Oct 24 2022

Jeffrey S Weber et al. found that combining CPI and mocetinostat had favorable response rates but with high levels of toxicity. [Read the Full Post]

Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia

0 | Oct 21 2022

William F Richter et al. defined alternative proliferation pathways that more directly derived from H3K79me2 loss. [Read the Full Post]

Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis

0 | Oct 14 2022

Thibaut Burg et al. suggested that HDAC inhibition was a potential new therapeutic strategy to modulate lipid metabolism defects in ALS and potentially other neurodegenerative diseases. [Read the Full Post]

Int J Oncol . 2022 Oct;61(4):114. doi: 10.3892/ijo.2022.5404. Epub 2022 Aug 3. Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors

103 | Oct 04 2022

Eriko Katsuta et al. found that JP11646 may thus be a possible treatment strategy for multiple types of solid cancers. [Read the Full Post]

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway

39 | Sep 30 2022

Xiao-Hu Zhou et al. found that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. [Read the Full Post]

Menin‑MLL inhibitors induce ferroptosis and enhance the anti‑proliferative activity of auranofin in several types of cancer cells

0 | Sep 27 2022

Ichiroh Kato et al. thought that the MI‑463‑induced decreased in cell viability might be at least partly associated with the inhibition of SCD1 activity. [Read the Full Post]

FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation

124 | Sep 23 2022

Amanda Blackmon et al. reviewed the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlighted key remaining questions. [Read the Full Post]

First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation

63 | Sep 13 2022

Kairui Yue et al. indicated that 35m could be a potential orally active therapeutic agent for the treatment of NLRP3-related diseases. [Read the Full Post]

Pharmacokinetic/pharmacodynamic modeling of roxadustat's effect on LDL cholesterol in patients in Japan with dialysis-dependent chronic kidney disease and anemia

25 | Sep 12 2022

Akitsugu Takada found that roxadustat could decrease LDL-C independent of statins and sevelamer. [Read the Full Post]

CRNDE acts as an epigenetic modulator of the p300/YY1 complex to promote HCC progression and therapeutic resistance

120 | Sep 11 2022

Yu-Chin Liu et al. supported the potential of targeting the CRNDE/p300/YY1 axis as a novel therapeutic strategy to overcome sorafenib resistance of HCC. [Read the Full Post]

HDAC3 Inhibitor RGFP966 Ameliorated Neuroinflammation in the Cuprizone-Induced Demyelinating Mouse Model and LPS-Stimulated BV2 Cells by Downregulating the P2X7R/STAT3/NF-κB65/NLRP3 Activation

38 | Sep 10 2022

Wei Sun et al. demonstrated that RFFP966 alleviated the inflammatory response and exerted a neuroprotective effect possibly by modulating P2X7R/STAT3/NF-κB65/NLRP3 signaling pathways. [Read the Full Post]

The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis

29 | Sep 04 2022

Adriana Celesia et al. found that ITF2357 targeted oncogenic BRAF in melanoma cells and induced a switch from autophagy to classic apoptosis, thus representing a possible candidate in melanoma targeted therapy. [Read the Full Post]

Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage

60 | Sep 04 2022

Paulina Pawelec et al. showed that Givinostat/ITF2357 did not prevent an inflammatory reaction after HI. [Read the Full Post]

Chronic AMPK Activation Reduces the Expression and Alters Distribution of Synaptic Proteins in Neuronal SH-SY5Y Cells

29 | Aug 29 2022

Alex J T Yang et al. suggested that chronic AMPK activation impacted synaptic protein content and reduced neurite protein abundance and distribution. [Read the Full Post]

Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection

11 | Aug 28 2022

Yaru Zhao et al. thought that BET/BRD4 could be considered as attractive host targets in antiviral drug discovery against ASFV. [Read the Full Post]

Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases

20 | Aug 24 2022

Valter Bergant et al. identified a bispecific MTr1/NSP16 inhibitor with anti-SARS-CoV-2 activity in vitro and in vivo but with unfavorable side effects. [Read the Full Post]

Inhibition of EZH2 suppresses peritoneal angiogenesis by targeting a VEGFR2/ERK1/2/HIF-1α-dependent signaling pathway

21 | Aug 23 2022

Yingfeng Shi et al. suggested that EZH2 might be a novel target for preventing peritoneal angiogenesis in PD patients. [Read the Full Post]

Design, Synthesis, and Biological Evaluations of DOT1L Peptide Mimetics Targeting the Protein-Protein Interactions between DOT1L and MLL-AF9/MLL-ENL

23 | Aug 22 2022

Yinan Yuan et al. found that inhibiting the protein-protein interactions between DOT1L and MLL fusion proteins was a potentially effective strategy for the treatment of MLL rearranged leukemias. [Read the Full Post]

In vitro and in vivo evaluation of kinase and protease inhibitors against Trypanosoma evansi

66 | Aug 21 2022

Wangchuk Dorjee Bhutia et al. showed that kinase inhibitors had higher potential to explore therapeutic molecules against surra organism. [Read the Full Post]

Discovery of Novel GMPS Inhibitors of Candidatus Liberibacter Asiaticus by Structure Based Design and Enzyme Kinetic

0 | Aug 21 2022

Jing Nan et al. suggested that folic acid and AZD1152 could be considered as promising candidates for the development of CLas agents. [Read the Full Post]

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

32 | Aug 18 2022

Bin Yuan et al. found that ferroptosis could be a potential therapeutic target for SAH, and SIRT1 activation was a promising method to inhibit ferroptosis. [Read the Full Post]

Salidroside Ameliorates Ultraviolet-Induced Keratinocyte Injury by Inducing SIRT1-Dependent Autophagy

42 | Aug 18 2022

Jin Ke et al. thought that SAL suppressed UVB-induced injury and autophagy by enhancing SIRT1 expression. [Read the Full Post]

Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects

39 | Aug 12 2022

Veruschka Albert et al. thought that a combined targeting of PKC and a subtype specific driver molecule might complement specified breast cancer treatment. [Read the Full Post]

Inhibiting SRC activity attenuates kainic-acid induced mouse epilepsy via reducing NR2B phosphorylation and full-length NR2B expression

40 | Aug 12 2022

Lu Liu et al. found that the early application of SRC inhibitors exerted protective effects on seizure severity, loss of neurons, and sprouting of mossy fibres in KA-induced mouse epilepsy. [Read the Full Post]

The CBP/β-Catenin Antagonist, ICG-001, Inhibits Tumor Metastasis via Blocking of the miR-134/ITGB1 Axis-Mediated Cell Adhesion in Nasopharyngeal Carcinoma

45 | Aug 11 2022

Luo Chen et al. showed that ICG-001 transient overexpression of miR-134 or stable overexpression of miR-134 could significantly reduce the lung metastasis of NPC cells. [Read the Full Post]

Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature

50 | Aug 08 2022

Jeries Abu-Hanna et al. suggested that inhibiting H3K27 demethylases held immense therapeutic potential in many diseases. [Read the Full Post]

Inhibition of CBP/β-catenin signaling ameliorated fibrosis in cholestatic liver disease

43 | Aug 07 2022

Masamichi Kimura et al. highlighted the therapeutic effect of CBP/β-catenin inhibition in cholestatic liver diseases. [Read the Full Post]

Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1

32 | Aug 07 2022

Jun Zhang found that antagomiR-34c-5p injection markedly elevated Sirt1 protein expression in CIH-stimulated mice. AntagomiR-34c-5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH-stimulated mice. [Read the Full Post]

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway

34 | Aug 06 2022

Chongqi Wei et al. revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application. [Read the Full Post]

Berberine encapsulated in exosomes derived from platelet-rich plasma promotes chondrogenic differentiation of the Bone Marrow Mesenchymal Stem Cells via the Wnt/β-catenin pathway

75 | Aug 05 2022

Bingjiang Dong et al. found that exos-Ber facilitated the differentiation of chondrogenic BMSCs by modulating the Wnt/β-catenin axis. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

152 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells

73 | Jul 26 2022

Lourdes González-Bermúdez et al. found that variations in H4K16Ac following the activation of the DNA damage response and aging point at this histone mark as a key mediator between DNA repair and age-associated chromatin alterations. [Read the Full Post]

Method for detecting acetylated PD-L1 in cell lysates by immunoprecipitation and western blot analysis

70 | Jul 26 2022

Frances Middleton-Davis et al. demonstrated that acetylation levels increase to 0.11-0.17% of total PD-L1 after a 4h treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). [Read the Full Post]

Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme

107 | Jul 22 2022

Pan Xie et al. constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provided new ideas for the treatment of GBM. [Read the Full Post]

AMPK-ChREBP axis mediates de novo milk fatty acid synthesis promoted by glucose in the mammary gland of lactating goats

85 | Jul 21 2022

Hengbo Shi et al. thought that glucose supplementation promoted de novo fatty acid synthesis via the AMPK-ChREBP axis, hence increasing milk fat yield in the goat mammary gland. [Read the Full Post]

Antifungal activity of dehydrocurvularin for Candida spp. through the inhibition of adhesion to human adenocarcinoma cells

85 | Jul 21 2022

Hitoshi Kamauchi et al. reported that dehydrocurvularin (1), isolated from the marine-derived fungus Curvularia aeria, exhibited anti-fungal activities for Candida albicans and Candida auris. [Read the Full Post]

Loss of METTL3 Attenuates Blastic Plasmacytoid Dendritic Cell Neoplasm Response to PRMT5 Inhibition via IFN Signalling

106 | Jul 17 2022

Malini Rethnam et al. implicated PRMT5 as a therapeutic target in BPDCN and provided insight into the involvement of METTL3 and interferon pathway in regulating response to PRMT5 inhibition. [Read the Full Post]

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

92 | Jul 16 2022

Jun Liu et al. found that the five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC. [Read the Full Post]

Parp Inhibition and Beyond in Brca- Associated Breast Cancer in Women: A State- Of- The- Art Summary of (Pre) - Clinical Research into Risk Reduction and Clinical Benefits

80 | Jul 15 2022

Ernest K J Pauwels et al. described the various causes of PARP inhibitor resistance as well as the research that indicated how to overcome phenomenon. [Read the Full Post]

Comparative Efficacy and Safety of Janus Kinase Inhibitors and Secukinumab in Patients with Active Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

189 | Jul 13 2022

Young Ho Lee suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo. [Read the Full Post]

Class Ⅰ histone deacetylase inhibitor regulate of Mycobacteria-Driven guanylate-binding protein 1 gene expression

163 | Jul 01 2022

Meili Wei et al. showed that the CpG site of the GBP1 promoter was hypermethylated, and the methylation status of the GBP1 promoter did not change significantly upon Mtb infection. [Read the Full Post]

Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies

171 | Jun 30 2022

Christine M Minnar et al. demonstrated that the combination of entinostat and NHS-IL12 therapy elicited potent antitumor activity. [Read the Full Post]

Repression of HIV-1 reactivation mediated by CRISPR/dCas9-KRAB in lymphoid and myeloid cell models

199 | Jun 26 2022

Lendel Correia da Costa et al. demonstrated that KRAB repressor protein was crucial to reactivation resistance phenotype. [Read the Full Post]

Histone Deacetylase Inhibitors Counteract CGRP Signaling and Pronociceptive Sensitization in a Rat Model of Medication Overuse Headache

168 | Jun 26 2022

Matteo Urru et al. provided evidence for a key role of HDACs and epigenetics in MOH pathogenesis, highlighting the therapeutic potential of HDAC inhibition in the prevention of migraine chronification. [Read the Full Post]

The PRC2 molecule EED is a target of epigenetic therapy for neuroblastoma

216 | Jun 23 2022

Dilibaerguli Shaliman et al. suggested that inhibitory cell cycle-regulated gene sets were markedly up-regulated. [Read the Full Post]

Real-world experience in treating pediatric relapsed/refractory or therapy-related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium

180 | Jun 22 2022

Eric S Schafer et al. found that therapy was well tolerated and effective in pediatric patients with R/R myeloid neoplasms, particularly those with epigenetic alterations, t-AML, and refractory disease. [Read the Full Post]

Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer

128 | Jun 19 2022

Leonie Ratz et al. identified a synthetic lethal interaction between EZH2 and ATM and proposed this synergistic interaction as a novel molecular combination for the treatment of BRCA1-mutant breast cancer. [Read the Full Post]

Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC)

173 | Jun 16 2022

Jessica L S Zylla et al. found that 4SC-202 treatment of tumors from a highly metastatic murine model of TNBC reduced metastasis and warrants further preclinical studies. [Read the Full Post]

Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

164 | Jun 15 2022

Yuebo Zhang et al. provided the molecular basis for a novel chemotherapy strategy for PDAC patients. [Read the Full Post]

Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor

156 | Jun 14 2022

Santhosh A Upadhyaya et al. discovered that single agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients. [Read the Full Post]

Discovery of precision targeting EZH2 degraders for triple-negative breast cancer

196 | Jun 13 2022

Cheng Wang et al. found that U3i could degrade PRC2 complex in TNBC cells, induce apoptosis, and cause little damage to normal cells. [Read the Full Post]

Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

375 | Jun 12 2022

Mohamed M Hammoud et al. revealed the antitumor potential of ferrocene derivative (10) through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

Exposure to escalating olaparib does not induce acquired resistance to PARPi and to other chemotherapeutic compounds in ovarian cancer cell lines

138 | Jun 10 2022

André Fedier et al. found that olaparib exposure was unlikely to produce an acquired resistance phenotype and that PARPi‑sensitive ovarian cancer cells were also cross‑sensitive to non‑platinum and even to compounds not directly interacting with the DNA. [Read the Full Post]

Review of second-generation androgen receptor inhibitor therapies and their role in prostate cancer management

118 | May 27 2022

Seyed Behzad Jazayeri et al. thought that olaparib and rucaparib had shown clinical benefit in heavily pretreated patients with mCRPC and DNA repair mutation genes. [Read the Full Post]

Evaluation of mitochondrial oxidative toxicity in mammalian cardiomyocytes by determining the highly reproducible and reliable increase in mitochondrial superoxides after exposure to therapeutic drugs

282 | May 27 2022

Dohee Ahn et al. found that a screening system using MitoSOX™ had the potential to be applied as a reliable biomarker for determining mitochondrial oxidative toxicity in new drug development. [Read the Full Post]

Imaging PARP with [ 18 F]rucaparib in pancreatic cancer models

104 | May 26 2022

Chung Ying Chan et al. demonstrated the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers. [Read the Full Post]

Long Noncoding RNA MALAT1 Promotes Laryngocarcinoma Development by Targeting miR-708-5p/BRD4 Axis to Regulate YAP1-Mediated Epithelial-Mesenchymal Transition

239 | May 25 2022

Xiaoqin Wu et al. thought that targeting MALAT1/miR-708-5p/BRD4 axis might provide a promising therapeutic strategy for laryngocarcinoma. [Read the Full Post]

Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers

132 | May 24 2022

Xuan Liu et al. indicated that the deep analysis of pre-treatment tumors could identify biomarkers that were predictive of response to talazoparib and potentially other PARP inhibitors. [Read the Full Post]

Talazoparib Dual-targeting on Poly (ADP-ribose) Polymerase-1 and -16 Enzymes Offers a Promising Therapeutic Strategy in Small Cell Lung Cancer Therapy: Insight from Biophysical Computations

113 | May 23 2022

Chwayita Mgoboza et al. found that binding residues with total binding energy greater than 1.00 kcal/mol contributed considerably to the Talazoparib's binding activities on PARP-1 and PARP-16. [Read the Full Post]

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

363 | May 20 2022

Patrick O Perche et al. thought that abrocitinib was an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who had not responded to systemic medications or when contraindicated otherwise. [Read the Full Post]

The antidepressant imipramine inhibits breast cancer growth by targeting estrogen receptor signaling and DNA repair events

136 | May 16 2022

Santosh Timilsina et al. designed an ongoing clinical trial, where they were testing the efficacy of imipramine for treating patients with triple-negative and estrogen receptor-positive breast cancer. [Read the Full Post]

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

0 | May 11 2022

Hyeon Young Park et al. suggested that treatment with a glutamine antagonist was a promising approach to prevent progression of atherosclerosis and restenosis. [Read the Full Post]

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

286 | May 10 2022

Xiaoli Yang et al. identified TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound could be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies. [Read the Full Post]

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)

349 | May 02 2022

Hidetoshi Hayashi et al. found that Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy. [Read the Full Post]

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis

211 | May 01 2022

Bram Verstockt et al. showed that Longitudinal monitoring of nuclear pSTAT3 in mucosal tissue compartments reflected distinctive on-target effects, independently of long-term treatment outcomes. [Read the Full Post]

Proangiogenesis effects of compound danshen dripping pills in zebrafish

154 | Apr 24 2022

Yang-Xi Hu et al. found that CDDP had a proangiogenic effect, the mechanism of which involved the VEGF/VEGFR and PI3K/AKT signaling pathways. [Read the Full Post]

Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ERα expression and proliferation in luminal primary and metastatic breast cancer cells

440 | Apr 20 2022

Sara Pescatori et al. thought that CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs. [Read the Full Post]

Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer

580 | Apr 19 2022

Yujun Hao et al. found that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors. [Read the Full Post]

Sotorasib Tackles KRASG12C-Mutated Pancreatic Cancer

245 | Apr 19 2022

Xinting Zheng et al. found that the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation. [Read the Full Post]

High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia

306 | Apr 15 2022

Emanuela M Ghia et al. found that Wnt5a-induced ROR1-signaling can enhance resistance to venetoclax therapy. [Read the Full Post]

B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer

308 | Apr 13 2022

Bin Zhou et al. found that B7-H4 expression was upregulated by STAT3 activation via PKCδ and played roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis might be a potential therapeutic target for CRC. [Read the Full Post]

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial

252 | Apr 13 2022

Georgina Angoa et al. showed that DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA. [Read the Full Post]

Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer's disease-related neuropathology in cell models

125 | Apr 12 2022

Siyi Zhang et al. not only showed that BRD4 was a novel epigenetic component that regulated BACE1 and Aβ levels, but also provided novel and translational insighted into the targeting of BRD4 for potential clinical applications. [Read the Full Post]

Inhibition of Bromodomain and Extra Terminal (BET) Domain Activity Modulates the IL-23R/IL-17 Axis and Suppresses Acute Graft- Versus-Host Disease

77 | Apr 08 2022

Katiri J Snyder et al. identified a role for BET proteins in regulating the IL-23R/STAT3/IL-17 pathway. [Read the Full Post]

The p300 inhibitor A-485 exerts antitumor activity in growth hormone pituitary adenoma

195 | Apr 07 2022

Chenxing Ji et al. found that inhibition of HAT p300 by its selective inhibitor A-485 was a promising therapy for GHPA. [Read the Full Post]

[Magnetic resonance imaging analysis on the effect of marathon on the dynamic changes of morphological characteristics of patellar tendon in amateur marathon runners after half marathon]

160 | Apr 06 2022

Y Zhang et al. thought that marathon had effect on the normal PT morphology in male amateur marathon runners, showing an increase in proximal CSA. [Read the Full Post]

JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis

286 | Apr 03 2022

Juhee Son et al. found that a limited but still promising utility of JIB-04 as an antiviral agent in the combat against COVID-19 and potentially other viral diseases. [Read the Full Post]

Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1

309 | Mar 25 2022

Tingwei Zhao et al. suggested that HDAC8 was a potential novel therapeutic target for heart failure accompanied by pathological lung diseases. [Read the Full Post]

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets

0 | Mar 23 2022

Juan Bayo et al. thought that the epigenetic alterations identified in HCC could be used to predict prognosis and to define a subgroup of high-risk patients that would potentially benefit from JmjC inhibitor therapy. [Read the Full Post]

AZD5153 reverses palbociclib resistance in ovarian cancer by inhibiting cell cycle-related proteins and the MAPK/PI3K-AKT pathway

294 | Mar 22 2022

Chen Liu et al. revealed that it was anticipated that this class of drugs, including AZD5153, which inhibited the cell cycle-related protein and MAPK/PI3K-AKT pathway, would exhibit synergistic effects with palbociclib in OC. [Read the Full Post]

Selinexor improves the anti-cancer effect of tucidinostat on TP53 wild-type breast cancer

341 | Mar 20 2022

Yingfang Shi et al. thought that the molecular mechanism might be through enhancing the activity of p53 in the nucleus of BC cells to suppress proliferation and invasion and promote apoptosis. [Read the Full Post]

What's new in myeloproliferative neoplasia

575 | Mar 19 2022

Stefan Schmidt et al. revealed components of the alarmin complex (S100A8 und S100A9) drove this local sterile inflammation process, which also represented a potential therapeutic target, as the S100A8 and A9 inhibitor Tasquinimod reduced fibrosis in a pre-clinical animal model. [Read the Full Post]

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

504 | Mar 18 2022

Theodoros Karantanos et al. implicated CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. [Read the Full Post]

Tubastatin A suppresses the proliferation of fibroblasts in epidural fibrosis through phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway

344 | Mar 12 2022

Yang Liu et al.discovered that Tub A could prevent epidural fibrosis formation by inhibiting fibroblast proliferation through mediating PI3K/AKT/mTOR pathway. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

657 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Recruitment of MLL1 complex is essential for SETBP1 to induce myeloid transformation

276 | Mar 11 2022

Nhu Nguyen et al. thought that the MLL1 complex played a critical role in Setbp1-induced transcriptional activation and transformation. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

665 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity

180 | Mar 08 2022

Dirk Brehmer et al. supported the continued clinical evaluation of JNJ-64619178 in patients with aberrant PRMT5 activity-driven tumors. [Read the Full Post]

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

415 | Mar 07 2022

Rameswari Chilamakuri et al. found that the dual inhibition of PI3K and HDAC by CUDC-907 was an effective therapeutic strategy for NB and other MYC-dependent cancers. [Read the Full Post]

Deacetylation of ZKSCAN3 by SIRT1 induces autophagy and protects SN4741 cells against MPP +-induced oxidative stress

194 | Mar 01 2022

Xian Wu et al. identified a novel acetylation-dependent regulatory mechanism of nuclear translocation of ZKSCAN3. [Read the Full Post]

AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia

177 | Feb 25 2022

Adrien Grenier et al. thought that selective AMPK-activating compounds kiledl AML cells by rewiring mitochondrial metabolism that primed mitochondria to apoptosis by BH3 mimetics, holding therapeutic promise in AML. [Read the Full Post]

Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

501 | Feb 23 2022

Matthew J Koster et al. showed that in this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. [Read the Full Post]

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries

354 | Feb 22 2022

Alexander Egeberg et al. emphasized that although these diseases had many overlaps in their pathogenesis, there was a need for an individualized treatment approach that considered the underlying disease, patient profile, and treatment history. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

407 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer

191 | Feb 20 2022

Daniel R Principe et al. suggested that XP-524 might benefit PDAC patients and warrant further exploration, particularly in combination with immune checkpoint inhibition. [Read the Full Post]

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

245 | Feb 07 2022

Mitsuhiro Kinoshita et al. suggested regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

372 | Jan 31 2022

Sean P Korpela et al. found that heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

936 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

Neutrophil Extracellular Traps Are Increased in Chronic Myeloid Leukemia and Are Differentially Affected by Tyrosine Kinase Inhibitors

362 | Jan 24 2022

Alona Telerman et al. thought that CML was associated with increased NET formation, which was augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML. [Read the Full Post]

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma

0 | Jan 23 2022

Xing Liu et al. found that PRMT5 promoted retinoblastoma growth, the PRMT5 inhibitor EPZ015666 inhibited retinoblastoma in vitro by regulating P53-P21/P27-CDK2 signaling pathways and slowed retinoblastoma growth in a xenograft model. [Read the Full Post]

Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4

197 | Jan 22 2022

Lu Zhao found that PRMT5 plays an important role in the invasion of AML, which acts via regulating the expression of LILRB4. PRMT5 could act as a potential therapeutic candidate for AML. Copyright © 2021 Lu Zhao et al. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

0 | Jan 12 2022

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Signaling Pathway of Histamine H 1 Receptor-Mediated Histamine H 1 Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells

259 | Jan 12 2022

Hiroyuki Mizuguchi et al. thought that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells was different from that in HeLa cells, possibly by using different promoters. [Read the Full Post]

Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis

0 | Jan 07 2022

Suresh Chava et al. found that DOT1L promoted ovarian cancer tumor growth by regulating apoptotic and metabolic pathways as well as NK cell-mediated eradication of ovarian cancer. [Read the Full Post]

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology

277 | Jan 05 2022

Natalia Sacilotto et al. highlighted significant differences in potency and selectivity among the clinical compounds with iadademstat being the most potent and revealed that most of the tool compounds had very low activity and selectivity. [Read the Full Post]

CYT387 Inhibits the Hyperproliferative Potential of Fibroblast-like Synoviocytes via Modulation of IL-6/JAK1/STAT3 Signaling in Rheumatoid Arthritis

423 | Jan 04 2022

Susmita Srivastava et al. found that CYT387 inhibits proliferation, migration, and pathogenic diseased potential of FLS isolated from adjuvant-induced arthritic (AA) rats via targeting IL-6/JAK1/STAT3 signaling cascade. [Read the Full Post]

A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer

457 | Jan 03 2022

Sukhmani K Padda et al. showed that the JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with EGFR-mutated NSCLC. [Read the Full Post]

Protective Effects of Hif2 Inhibitor PT-2385 on a Neurological Disorder Induced by Deficiency of Irp2

279 | Dec 29 2021

Jiaqi Shen et al. found that Irp2 depletion-induced Hif2α was, in vivo, in charge of the switch between OXPHOS and glycolysis. [Read the Full Post]

HO-1 promotes resistance to an EZH2 inhibitor through the pRB-E2F pathway: correlation with the progression of myelodysplastic syndrome into acute myeloid leukemia

237 | Dec 26 2021

Zhengchang He et al. found that HO-1 could influence MDS resistance and progression to AML. [Read the Full Post]

4-Acyl Pyrrole Capped HDAC Inhibitors: A New Scaffold for Hybrid Inhibitors of BET Proteins and Histone Deacetylases as Antileukemia Drug Leads

460 | Dec 22 2021

Linda Schäker-Hübner et al. suggested an advantage of dual HDAC/BET inhibitors over the combination of two single targeted compounds. [Read the Full Post]

High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors

241 | Dec 16 2021

Tatjana Ullmann et al. found that I-BET151 and HDAC inhibitors simultaneously upregulated the mRNA expression of pro-inflammatory IL-1ß. [Read the Full Post]

Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins

156 | Dec 15 2021

Jiacheng Lai et al. showed that the research on the anticancer mechanism of I-BET151 would lead to new treatment strategies for clinical cancer. [Read the Full Post]

Biological Effects of BET Inhibition by OTX015 (MK-8628) and JQ1 in NPM1-Mutated (NPM1c) Acute Myeloid Leukemia (AML)

360 | Dec 13 2021

Hanane Djamai et al. found that BETi, similar to ATO + ATRA, induced differentiation and apoptosis which was TP53 independent in the NPM1c cell line OCI-AML3 and primary cells. [Read the Full Post]

Medium & long-chain acylcarnitine's relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study

355 | Dec 10 2021

Dan-Meng Zheng et al. found that C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine. [Read the Full Post]

Downregulation of AMPK dependent FOXO3 and TFEB involves in the inhibition of autophagy in diabetic cataract

418 | Dec 09 2021

Jiani Li et al. thought that targeting AMPK-induced autophagy might be a potential therapeutic approach for diabetic cataract. [Read the Full Post]

Regulation of NADPH Oxidase-Mediated Superoxide Production by Acetylation and Deacetylation

492 | Dec 08 2021

Ning Xia et al. found that both SIRT1 and non-sirtuin deacetylases played a role in regulating NADPH oxidase activity. [Read the Full Post]

Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities

424 | Dec 07 2021

Ananda Chowdhury et al. thought that the proposed self-assembly process might present a simple alternative to more sophisticated delivery modalities. [Read the Full Post]

The histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting TLR2/MyD88 and HDAC3/ NF-κB p65-mediated neuroinflammation

452 | Dec 03 2021

Yanjia Shen et al. found that belinostat ameliorated EAE in mice through inhibiting neuroinflammation via suppressing M1 microglial polarization. [Read the Full Post]

Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model

495 | Dec 03 2021

Jessica V Kaczmarek et al. thought that Belinostat might therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma. [Read the Full Post]

Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [ 111 In]In-DOTATATE Uptake in NET Cells

577 | Nov 30 2021

Maria J Klomp rt al. suggested that proper timing of HDACi treatment was most likely essential for a beneficial outcome. [Read the Full Post]

Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells

643 | Nov 29 2021

Yichen Zhang et al. revealed that butyrate treatment had the capacity to increase the number of beta cells, which might be predominantly mediated through its HDAC inhibitory activity. [Read the Full Post]

Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia

400 | Nov 27 2021

William F Richter et al. found that this pathway also depends on MLL1, indicating combinations of DOT1L, MLL1 and FLT3 inhibitors should be explored for treating FLT3-mutant leukemia. [Read the Full Post]

Pim kinase inhibitor co-treatment decreases alternative non-homologous end-joining DNA repair and genomic instability induced by topoisomerase 2 inhibitors in cells with FLT3 internal tandem duplication

461 | Nov 12 2021

Mario Scarpa et al. found that Pim kinase inhibitor co-treatment both enhanced TOP2 inhibitor cytotoxicity and decreased TOP2 inhibitor-induced genomic instability in cells with FLT3-ITD. [Read the Full Post]

The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

519 | Nov 09 2021

Simona Moravcová et al. suggested that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerated or hampered the process of NA-induced AANAT activation or affected the AANAT enzyme stability. [Read the Full Post]

Menin‑MLL inhibitors induce ferroptosis and enhance the anti‑proliferative activity of auranofin in several types of cancer cells

789 | Nov 05 2021

Ichiroh Kato et al. thought that menin‑MLL inhibitors, such as MI‑463, in combination with auranofin represented an effective therapeutic approach for several types of cancer via the induction of ferroptosis. [Read the Full Post]

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells

430 | Nov 01 2021

Punit Saraon et al. found that targeting of COPB2 with EMI66 presented a viable approach to attenuate mutant EGFR signalling and growth in NSCLC. [Read the Full Post]

Small-molecule compounds boost genome-editing efficiency of cytosine base editor

577 | Oct 23 2021

Tianyuan Zhao et al. provided a new strategy to improve the activity and specificity of CBE in human cells. Ricolinostat and Nexturastat A augment the effectiveness and applicability of CBE. [Read the Full Post]

Roxadustat (FG-4592) protects against ischemia/reperfusion-induced acute kidney injury through inhibiting the mitochondrial damage pathway in mice

486 | Oct 21 2021

Mei Zhang et al. found that pretreatment with FG-4592 might effectively prevent kidney from IRI possibly by via diminishing tubular cells injuries and protection of mitochondrial damage pathway. [Read the Full Post]

C646 Protects Against DSS-Induced Colitis Model by Targeting NLRP3 Inflammasome

478 | Oct 20 2021

Xueming Xu et al. demonstrated the ability of C646 to suppress the NLRP3 inflammasome activity and its potential application in the treatment of inflammatory bowel disease. [Read the Full Post]

HDAC3 inhibitor suppresses endothelial-to-mesenchymal transition via modulating inflammatory response in atherosclerosis

556 | Oct 19 2021

Lifang Chen et al. suggested that HDAC3 inhibitor suppressed EndMT via modulating inflammatory response in ApoE-/- mice and HUVECs. [Read the Full Post]

Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy

636 | Oct 13 2021

Marco Spreafico et al. provided evidence of HDAC8 overexpression in DMD patients and zebrafish and supported its specific inhibition as a new valuable therapeutic approach in the treatment of this pathology. [Read the Full Post]

Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis

567 | Oct 12 2021

He-Ming Huang et al. found that givinostat was efficacious in reversing diet-induced NASH, and might serve as a therapeutic agent for the treatment of human NASH. [Read the Full Post]

Structural basis of the selective activation of enzyme isoforms: Allosteric response to activators of β1- and β2-containing AMPK complexes

853 | Oct 06 2021

Elnaz Aledavood et al. found the design of activators tailored for improving the therapeutic treatment of tissue-specific metabolic disorders. [Read the Full Post]

Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition

268 | Oct 04 2021

Stephan J Matissek et al. identified BET inhibitors as effective therapy for WM, and these inhibitors could be enhanced in combination with BCL2 or histone deacetylase inhibition. [Read the Full Post]

Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

327 | Sep 29 2021

Eva Lhuissier et al. found that DZNep exposure could presensitize chondrosarcoma cells to a standard anticancer drug. [Read the Full Post]

Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis

498 | Sep 28 2021

Suresh Chava et al. demonstrated that DOT1L promoted ovarian cancer tumor growth by regulating apoptotic and metabolic pathways as well as NK cell-mediated eradication of ovarian cancer and identified DOT1L as a new pharmacological target for ovarian cancer therapy. [Read the Full Post]

Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands

430 | Sep 27 2021

Abeer K Shaalan et al. found AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis. [Read the Full Post]

Discovery of Novel GMPS Inhibitors of Candidatus Liberibacter Asiaticus by Structure Based Design and Enzyme Kinetic

483 | Sep 27 2021

Jing Nan et al. suggested that folic acid and AZD1152 could be considered as promising candidates for the development of CLas agents. [Read the Full Post]

Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models

495 | Sep 23 2021

Wen-Li Dong et al. thought that the mechanisms underlying ROF neuroprotective effects appeared to be associated with NAD+/SIRT1-dependent activation of lysosomal function. [Read the Full Post]

Sodium tanshinone IIA sulfonate attenuates cigarette smoke extract-induced mitochondrial dysfunction, oxidative stress and apoptosis in alveolar epithelial cells by enhancing SIRT1 pathway

342 | Sep 23 2021

Ruijuan Guan et al. found that STS ameliorated CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. [Read the Full Post]

Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures

563 | Sep 17 2021

Giulia Franciosa et al. highlighted the potential of proteomics to dissect alterations in cellular signaling and identified druggable pathways in cancer. [Read the Full Post]

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

607 | Sep 16 2021

Shan Zhou et al. showed CB2 played a central role in renal tubular mitochondrial dysfunction and kidney ageing. [Read the Full Post]

Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study

407 | Sep 14 2021

Yen-Hao Chen et al. found that UTX played an important role in the process of OTSCC and overexpression of UTX might predict poor prognosis in OTSCC patients who received surgical resection. [Read the Full Post]

SRT1720 inhibits the growth of bladder cancer in organoids and murine models through the SIRT1-HIF axis

585 | Sep 13 2021

Ping Tan et al. demonstrated the power of cancer organoid-based drug discovery and, in principle, identified SRT1720 as a new treatment for bladder cancer. [Read the Full Post]

Tumor-promoting function of PIMREG in glioma by activating the β-catenin pathway

552 | Sep 12 2021

Dekang Wang et al. provided new insights into the molecular mechanism for glioma pathogenesis and treatment. [Read the Full Post]

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aβ Transport Across the Blood-brain Barrier in Alzheimer's Disease

716 | Sep 11 2021

Rui Zhou et al. found that high cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aβ transport disorder in the blood-brain barrier. [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1373 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1

641 | Sep 01 2021

Hong Luo et al. found the therapeutic potential for targeting CHFR-ZEB1 signaling in resistant malignant breast cancers. [Read the Full Post]

Oncolytic Bovine Herpesvirus 1 Inhibits Human Lung Adenocarcinoma A549 Cell Proliferation and Tumor Growth by Inducing DNA Damage

578 | Sep 01 2021

Wencai Qiu et al. thought that BoHV-1 had oncolytic effects against human lung adenocarcinoma in vivo. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

0 | Aug 29 2021

Christine Song et al.found an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport

757 | Aug 27 2021

Changhong Ren et al. suggested that supplemental activation of glucose transport after CCH might provide a clinically applicable intervention for improving cognitive impairment. [Read the Full Post]

Myelocytomatosis-Protein Arginine N-Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma

483 | Aug 24 2021

Yuhong Luo et al. revealed that PRMT5 was an epigenetic executer of MYC, leading to repression of the transcriptional regulation of downstream genes that promoted hepatocellular carcinogenesis. [Read the Full Post]

Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations

640 | Aug 23 2021

Jing Xu et al. found that veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. [Read the Full Post]

Poly (ADP-Ribose) Polymerase Inhibitor, ABT888, Improved Cisplatin Effect in Human Oral Cell Carcinoma

625 | Aug 23 2021

Irene Paterniti et al. indicated PARP inhibitors as adjuvants for therapeutic strategy of oral cancer. [Read the Full Post]

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor

977 | Aug 20 2021

Qing Yan et al. thought that tofacitinib could suppress T cell activation by upregulating TGFβRI expression, which provided a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients. [Read the Full Post]

HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer

772 | Aug 06 2021

Miranda E Clements et al. suggested HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer. [Read the Full Post]

Phase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone Deacetylase Inhibitor, in Chinese Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer

839 | Aug 06 2021

Jiani Wang et al. found that entinostat with exemestane showed reasonable safety, tolerability, and encouraging efficacy in Chinese patients with HR+/HER2- MBC. [Read the Full Post]

Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs

994 | Aug 03 2021

Chia-Lung Yang et al. established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which had good therapeutic effects but do not cause severe side effects. [Read the Full Post]

High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas

1030 | Aug 02 2021

Philip D Tatman et al. suggested an important role of HDACs in meningioma biology and as a targetable mechanism. [Read the Full Post]

Effect of Decitabine (5-aza-2'-deoxycytidine, 5-aza-CdR) in Comparison with Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) on DNMT1, DNMT3a and DNMT3b, HDAC 1-3, SOCS 1, SOCS 3, JAK2, and STAT3 Gene Expression in Hepatocellular Carcinoma HLE and LCL-PI 11 Cell Lines

738 | Jul 31 2021

Masumeh Sanaei et al. found that 5-Aza-CdR and SAHA could induce cell growth inhibition and apoptosis induction through the JAK/STAT pathway. [Read the Full Post]

TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer

479 | Jul 28 2021

Tao Gui et al. found that TCF3 functions as a tumor suppressor epigenetically silenced by EZH2 and DNMT3B in EC. [Read the Full Post]

4sc-202 and Ink-128 cooperate to reverse the epithelial to mesenchymal transition in OSCC

562 | Jul 25 2021

Xi Yang et al. identified an effective combination therapy involving class I histone deacetylase and mammalian target of rapamycin complex 1/2 inhibition that effectively blocked the EMT of tumor cells by upregulating FoxO1 expression to inhibit Twist1 transcription. [Read the Full Post]

Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies

665 | Jul 23 2021

Kian-Huat Lim et al. thought that the combination of alisertib and nab-paclitaxel had manageable side-effect profile and showed promising preliminary efficacy in high-grade NETs, warranting further testing. [Read the Full Post]

Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing

620 | Jul 23 2021

Yaman Tayyar et al. found that both RT and Alpelisib significantly improved Alisertib-mediated tumor killing. [Read the Full Post]

CDKN2A Determines Mesothelioma Cell Fate to EZH2 Inhibition

508 | Jul 22 2021

Giulia Pinton et al. found that the expression of CDKN2A predicted cell fate in response to EZH2 inhibition and could potentially stratify tumors likely to undergo apoptosis. [Read the Full Post]

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

1233 | Jul 21 2021

Eman Y Ahmed et al. found that 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. [Read the Full Post]

Cost-effectiveness analysis of olaparib and niraparib as maintenance therapy for women with recurrent platinum-sensitive ovarian cancer

521 | Jul 20 2021

John Hang Leung et al. showed that olaparib was considered to be a cost-effective maintenance therapy for patients with recurrent platinum-sensitive ovarian cancer from the Taiwan NHIA perspective. [Read the Full Post]

Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system

404 | Jul 08 2021

Rachel V Hatch et al. suggested that PARPi therapy was associated with numerous toxicities that were best managed through a multi-modal approach. [Read the Full Post]

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy

1158 | Jul 08 2021

Ioannis M Koukourakis et al. found that the combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy had acceptable toxicity and was highly effective in eradicating metastatic lesions. [Read the Full Post]

Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells

601 | Jul 07 2021

Md Hafiz Uddin found that KPT-8602 with or without olaparib was shown to reduce homologous recombination-regulated DNA damage response targets including BRCA1, BRCA2, CHEK1, EXO1, BLM, RAD51, LIG1, XRCC3 and RMI2. [Read the Full Post]

The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell-lines

670 | Jul 06 2021

Kate E Lines et al. thought that reducing CaSR expression might be a viable option in the treatment of pituitary tumours. [Read the Full Post]

Research progress of PARP inhibitor monotherapy and combination therapy for endometrial cancer

499 | Jul 05 2021

Ke Shen et al. found that PARP inhibitors played an important role in killing tumor cells with defects in homologous recombination repair. [Read the Full Post]

Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study

438 | Jul 04 2021

Yoichi Naito et al. showed that single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. [Read the Full Post]

Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: A case report

761 | Jun 30 2021

Fu Ming Zi et al. found that Ruxolitinib could be used as an alternative therapeutic approach for severe and refractory CRS without impairing CAR-T amplification and anti-tumor effect. [Read the Full Post]

PARP and CDK4/6 inhibitor combination therapy induces apoptosis and suppresses neuroendocrine differentiation in prostate cancer

496 | Jun 24 2021

Cheng Wu et al. provided a molecular rationale for PARPi and CDK4/6i combination therapy and revealed mechanism-based clinical trial opportunities for men with NEPC. [Read the Full Post]

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

633 | Jun 19 2021

Hyeon Young Park et al. found that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis. [Read the Full Post]

HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes

699 | Jun 18 2021

Varvara Maksimova et al. showed that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivated epigenetically silenced genes, probably by affecting DNA methylation. [Read the Full Post]

Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

946 | Jun 08 2021

Rafael Rubiera-Pebe et al. showed that afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs. [Read the Full Post]

Tofacitinib Therapy in Children and Young Adults with Pediatric-Onset Medically-Refractory Inflammatory Bowel Disease

561 | Jun 07 2021

Hillary Moore et al. found that tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. [Read the Full Post]

High response rate and durability driven by HLA genetic diversity in kidney cancer patients treated with the immunotherapy combination lenvatinib and pembrolizumab

409 | May 28 2021

Chung-Han Lee et al. identified lenvatinib plus pembrolizumab as a highly active treatment strategy in RCC and reveal HLA-I diversity as a critical determinant of efficacy for this combination. [Read the Full Post]

Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice?

1209 | May 21 2021

Athanasios Mavratzas et al. thought that treatment of metastatic luminal breast cancer after progression on CDK4/6 inhibitors remained a challenge. [Read the Full Post]

SMALL MOLECULE IMAGING AGENT FOR MUTANT KRAS G12C

463 | May 19 2021

Peter D Koch et al. found that two fluorescent derivatives (BODIPY FL and BODIPY TMR) of ARS-1323 bind mutant KRAS and could be used for biochemical binding screens. [Read the Full Post]

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

841 | May 17 2021

Silvia Mola et al. found that TAMs were a driving force for MPM growth, progression, and resistance to tazemetostat. [Read the Full Post]

Ibrutinib-induced acute kidney injury via interstitial nephritis

468 | May 12 2021

Csilla Markóth et al. concluded that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib could cause acute interstitial nephritis. [Read the Full Post]

Development and validation of an MRI-based radiomics nomogram for distinguishing Warthin's tumour from pleomorphic adenomas of the parotid gland

689 | May 07 2021

Ying-Mei Zheng et al. found that the MRI-based radiomics nomogram had good performance in distinguishing parotid WT from PMA, which could optimize clinical decision-making. [Read the Full Post]

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

497 | May 06 2021

Shuiyan Wu et al. thought that the BRD4 degrader ARV-825 could effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

600 | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment

248 | Apr 30 2021

Sophia Thy et al. thought that BETi could be used to "episensitize" UC cells to cytotoxic chemotherapy and inhibitors of DNA repair by inducing BRCAness in non BRCA1/2 mutated cancers. [Read the Full Post]

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib

334 | Apr 29 2021

Xiao-Ru Zhou et al. provided a promising combination therapy for MCL and highlighted the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor. [Read the Full Post]

MLL1 combined with GSK3 and MAP2K inhibition improves the development of in vitro-fertilized embryos

527 | Apr 27 2021

Xuejie Han et al. found that the application of 3i provided a new method for improving IVF embryo production in domestic animals. [Read the Full Post]

H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

585 | Apr 25 2021

Jessica Connacher et al. found that H3K36me2&3-associated repression of genes was therefore involved in key transcriptional shifts that accompanied the transition from early gametocyte differentiation to intermediate development. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1065 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

492 | Apr 15 2021

Jung Yoo et al. found synergy between paclitaxel and HDAC6-selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6-selective inhibitors, not only in ovarian cancer but also in other tumors. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1460 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat

384 | Apr 14 2021

Chung-Pu Wu et al. suggested that the co-administration of citarinostat with a non-toxic modulator of ABCB1 and ABCG2 might optimize its therapeutic application in the clinic. [Read the Full Post]

The clinical significance of histone deacetylase-8 in human breast cancer

504 | Apr 13 2021

Golebagh Rahmani et al. highlighted the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy. [Read the Full Post]

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets

793 | Apr 11 2021

Juan Bayo et al. found that mutations and changes in expression of epigenetic modifiers were common events in human hepatocellular carcinoma, leading to an aggressive gene expression program and poor clinical prognosis. [Read the Full Post]

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function

519 | Apr 10 2021

Adam P Cribbs et al. found that compelling argument for further clinical investigation. [Read the Full Post]

Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

482 | Apr 07 2021

Mu-Chen Zhang et al. found that CR-CHOP was effective and safe in elderly patients with newly diagnosed DLBCL. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

878 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

954 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells

192 | Mar 30 2021

Xueyuan Cheng et al. found that the combination treatment inhibits cell viability, formation of colonies, increased apoptosis and cell cycle arrest at G0-G1. [Read the Full Post]

Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy

518 | Mar 24 2021

Zhonghai Shen et al. thought that HDAC6 inhibition prevented OA development, and HDAC6 could be applied as a potential therapeutic target for OA management. [Read the Full Post]

Oxidative stress abrogates the degradation of KMT2D to promote degeneration in nucleus pulposus

449 | Mar 23 2021

Wenbin Xu et al. approved that oxidative stress induced ROS production promote the process of NP degeneration by enhancing KMT2D mediated transcriptional regulation of matrix degeneration related genes during NP degeneration. [Read the Full Post]

Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity

391 | Mar 21 2021

Kongkai Zhu et al. described the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. [Read the Full Post]

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

547 | Mar 19 2021

Seiichi Okabe et al. suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors. [Read the Full Post]

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors

464 | Mar 12 2021

Sailu Sarvagalla et al. found that a possible means to develop sub-type selective inhibitor was by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. [Read the Full Post]

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

408 | Mar 12 2021

Nina Schmid et al. found that several SIRTs were expressed by GCTs, and SIRT1 and SIRT3 were involved in the growth regulation of KGN. [Read the Full Post]

A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival

398 | Mar 11 2021

Yvonne de Jong et al. thought that AURKA, CHK1 and PLK1 were identified as important survival genes in chondrosarcoma cell lines. [Read the Full Post]

Sublethal irradiation promotes the metastatic potential of hepatocellular carcinoma cells

354 | Mar 08 2021

Yulin Cao et al. indicated that MMP-8 secreted by irradiated NPCs enhanced the migration and invasion of HCC by regulating AMPK/mTOR signaling, revealing a novel mechanism mediating sublethal irradiation-induced HCC metastasis at the level of the tumor microenvironment. [Read the Full Post]

Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

806 | Mar 05 2021

Yoshifumi Tada et al. found that baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. [Read the Full Post]

In-vitro evaluation of the immunomodulatory effects of baricitinib: implication for COVID-19 therapy

838 | Mar 04 2021

Linda Petrone et al. found that exogenous addition of baricitinib decreased the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. [Read the Full Post]

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

358 | Mar 02 2021

Xiaowen Bi et al. suggested that CBP bromodomain could serve as a candidate therapeutic target for the treatment of lethal sepsis via inhibiting LPS-induced expression and release of HMGB1 and suppressing the pro-inflammatory activity of HMGB1. [Read the Full Post]

Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

450 | Feb 16 2021

Lotta Pohjolainen et al. showed similar hypertrophic responses to PKC modulators in NRVMs and hiPSC-CMs. [Read the Full Post]

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

627 | Feb 07 2021

Qiang Liu et al. suggested that SLP-2 controlled the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1335 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer

386 | Jan 31 2021

Ziyi Sun et al. found that PIM1 was a poor prognostic factor for NSCLC. [Read the Full Post]

Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis

606 | Jan 30 2021

Thomas M Hofbaue et al. found mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components. [Read the Full Post]

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma

525 | Jan 29 2021

Xing Liu et al. found that EPZ015666 inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. [Read the Full Post]

Inhibition of PRMT5 Attenuates Oxidative Stress-Induced Pyroptosis via Activation of the Nrf2/HO-1 Signal Pathway in a Mouse Model of Renal Ischemia-Reperfusion Injury

447 | Jan 29 2021

Changhui Diao et al. thought that PRMT5 might be a promising therapeutic target. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

567 | Jan 22 2021

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules

510 | Jan 22 2021

Ji-Sheng Wang et al. found that "leech-centipede" medicine could improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protected endothelial function and anti-platelet activation. [Read the Full Post]

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer

547 | Jan 17 2021

R Vatapalli et al. thought that DOT1L selectively regulated the tumorigenicity of AR-positive prostate cancer cells and was a promising therapeutic target for PCa. [Read the Full Post]

Targeting LSD1 for acute myeloid leukemia (AML) treatment

510 | Jan 14 2021

Shujing Zhang et al. discussed the main epigenetic drugs targeting LSD1 for AML therapy. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

652 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

750 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [Read the Full Post]

Effects and Mechanism of Action of PX-478 in Oxygen-Induced Retinopathy in Mice

506 | Jan 07 2021

Xiaoyan Pan et al. found that HIF-1α played a main role in OIR and could be considered a therapeutic target in OIR by suppressing downstream angiogenic factors, PX-478 decreasing the retinal avascular area and NV. [Read the Full Post]

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

537 | Jan 01 2021

Ahlam Ali et al. found that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC. [Read the Full Post]

Pan- and Isoform-specific Inhibition of the Bromodomain and Extra-terminal Proteins and Evaluation of Synergistic Potential With Entospletinib in Canine Lymphoma

448 | Dec 27 2020

Weibo Kong et al. showed that Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET. [Read the Full Post]

Small molecular compounds efficiently convert human fibroblasts directly into neurons

0 | Dec 26 2020

Jijuan Yang et al. found that a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons. [Read the Full Post]

Targeted therapy of TERT-rearranged neuroblastoma with BET bromodomain inhibitor and proteasome inhibitor combination therapy

182 | Dec 24 2020

Jingwei Chen et al. showed that OTX015 and carfilzomib combination therapy was likely to be translated into the first clinical trial of a targeted therapy in TERT-rearranged neuroblastoma patients. [Read the Full Post]

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells

454 | Dec 22 2020

Xuejian Zhou et al. indicated that Artesunate induced autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells. [Read the Full Post]

AMPK mediates energetic stress-induced liver GDF15

490 | Dec 21 2020

Logan K Townsend et al. proved that AMPK played a role in mediating the induction of GDF15 under conditions of energetic stress in mouse liver in vivo. [Read the Full Post]

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

469 | Dec 20 2020

Zhenghui Huang et al. found that PfHDAC1 was a potential drug target for overcoming multidrug resistance and that JX21108 treated malaria and blocked parasite transmission simultaneously. [Read the Full Post]

HDAC Inhibition Increases HLA Class I Expression in Uveal Melanoma

428 | Dec 19 2020

Zahra Souri et al. found that epigenetic drugs (in this case an HDAC inhibitor) may influence the expression of immunologically relevant cell surface molecules in UM, demonstrating that these drugs potentially influence immunotherapy. [Read the Full Post]

Histone Deacetylase Inhibitors and Papillary Thyroid Cancer

586 | Dec 16 2020

Eleftherios Spartalis et al. showed that HDACIs had no significant effect as monotherapy against PTC but further research needed to be conducted in order to investigate their potential effect when used as an additional modality. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzyme by Belinostat: Implications for Drug-Drug Interactions

515 | Dec 15 2020

Xiaoyu Wang et al. indicated that the intravenous infusion of belinostat at clinical available dose could contribute a significant increase to the AUC of co-administrated drugs primarily cleared by UGT1A3 or UGT1A1. [Read the Full Post]

Design, synthesis and evaluation of novel indirubin-based N-hydroxybenzamides, N-hydroxypropenamides and N-hydroxyheptanamides as histone deacetylase inhibitors and antitumor agents

550 | Dec 12 2020

Duong Tien Anh et.al found that the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development. [Read the Full Post]

Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload

691 | Dec 12 2020

Hanna Jung et al. indicated that MGCD, an HDAC inhibitor, attenuated aortic remodeling in rats with TAC-induced pressure overload rats and might serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases. [Read the Full Post]

Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of MLL-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML

389 | Dec 09 2020

Annalisa Lonetti et al. highlighted a novel therapeutic strategy for pediatric AML patients. [Read the Full Post]

HDAC6-selective inhibitors decrease nerve-injury and inflammation-associated mechanical hypersensitivity in mice

490 | Dec 02 2020

Farhana Sakloth et al. suggested that inhibition of HDAC6 provided a promising therapeutic avenue for the alleviation of mechanical allodynia associated with peripheral nerve injury and peripheral inflammation. [Read the Full Post]

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

673 | Nov 22 2020

Sabina Luszczak et al. believed that a co-targeting approach was a viable therapeutic strategy that should be developed further in pre-clinical studies. [Read the Full Post]

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

1473 | Nov 18 2020

Isabella J Brouwer et al. suggested that STAT3 played a preferential role in the mechanism of action of these cucurbitacins. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Nov 14 2020

Laurie K Svoboda et al. demonstrated that the SSP was highly active in Ewing sarcoma and that its oncogenic activation was maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Activating JAK-mutations confer resistance to FLT3 kinase inhibitors in FLT3-ITD positive AML in vitro and in vivo

470 | Nov 10 2020

Christoph Rummelt et al. characterized a novel mechanism of resistance to FLT3-ITD inhibition and might offer a potential therapy, using dual JAK and FLT3 inhibition. [Read the Full Post]

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGFß and EGFR signaling pathways in obstructive nephropathy

462 | Oct 28 2020

Xingying Chen et al. indicated that HDAC6 inhibition could attenuate development of renal fibrosis by suppression of TGFb1 and EGFR signaling, and suggested that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis. [Read the Full Post]

Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways

506 | Oct 26 2020

Guangfeng Long et al.found that the protective effect of FG-4592 on DOX-induced cardiotoxicity possibly through upregulating HIF-1α and its target genes antagonizing apoptosis and oxidative stress. [Read the Full Post]

Piceatannol reduces resistance to statins in hypercholesterolemia by reducing PCSK9 expression through p300 acetyltransferase inhibition

442 | Oct 25 2020

Hyo-Jin Kim et al. indicated that PT was a new nutraceutical candidate to reduce the statin resistance and tolerance that occured in patients with hypercholesterolemia. [Read the Full Post]

Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis

454 | Oct 23 2020

Fang Chen et al.found that HDAC3 aberration and the subsequent Klotho suppression constituted an important regulatory loop that promotes MTD and renal fibrosis and uses of HDAC3-selective inhibitors were potentially effective in treating renal fibrotic disorders. [Read the Full Post]

HDAC3 Regulates Gingival Fibroblast Inflammatory Responses in Periodontitis

456 | Oct 15 2020

K B Lagosz et al. identified HDAC3 as an important regulator of inflammatory gene expression in GFs and suggested that therapeutic targeting of HDAC activity, in particular HDAC3, may be clinically beneficial in suppressing inflammation in periodontal disease. [Read the Full Post]

Development of Artificial Plasma Membranes Derived Nanovesicles Suitable for Drugs Encapsulation

462 | Oct 14 2020

Carolina Martinelli et al.documented the possibility to easily generate scalable nanovesicles with specific therapeutic cargo modifications useful in different drug delivery contexts. [Read the Full Post]

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

515 | Oct 02 2020

Nicholas D LeBlond et al. suggested that intervention with the first-generation AMPK activator A-769662 was not able to stem the progression of atherosclerosis. [Read the Full Post]

Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors

192 | Sep 29 2020

Qifei Li et al. supported that this novel compound 13f provided a perspective for developing effective BRD4 inhibitors. [Read the Full Post]

CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR

201 | Sep 24 2020

Adhikarimayum Lakhikumar Sharma et al. demonstrated that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. [Read the Full Post]

AGE-Induced Suppression of EZH2 Mediates Injury of Podocytes by Reducing H3K27me3

228 | Sep 23 2020

Marita Liebisch et al. provided a novel pathway how AGEs contributed to podocyte injury and the formation of the so-called metabolic memory in DKD. [Read the Full Post]

Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia

479 | Sep 22 2020

Yitao Huang et al. presented a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions. [Read the Full Post]

Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis

329 | Sep 21 2020

Rajesh K Kasam et al. provided important proof-of-concept that demonstrated barasertib as a possible intervention therapy for IPF. [Read the Full Post]

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets

433 | Sep 21 2020

Julia Krushkal et al. indicated potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggested targets for combination therapies. [Read the Full Post]

Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes

445 | Sep 16 2020

Yingjie Wang et al. suggested the Mst1-AMPK-Sirt1 axis was a potential target for RA therapy. [Read the Full Post]

SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway

465 | Sep 16 2020

Yangyang Li et al. proposed that the discovery of the effect of SIRT1 on neuropathic pain in the VTA represented an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway. [Read the Full Post]

Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells

769 | Sep 10 2020

Kazuki Okubo et al. found that there was a positive feedback cycle among AMPK activation, histone acetylation, and ER stress induction. [Read the Full Post]

Sotrastaurin, a PKC inhibitor, attenuates RANKL-induced bone resorption and attenuates osteochondral pathologies associated with the development of OA

474 | Sep 08 2020

Cong Pang et al. provided evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. [Read the Full Post]

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing

523 | Aug 31 2020

Frank M Davis et al. concluded that palmitate contributed to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy might represent a novel treatment for nonhealing diabetic wounds. [Read the Full Post]

Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells

450 | Aug 30 2020

Maria Wiese et al. found that combinatorial treatment with CBP and BET inhibitors was highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy. [Read the Full Post]

Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic β-cells

564 | Aug 30 2020

Ye-Jee Lee et al. suggested that SIRT1 was a potential target for the protection of pancreatic β-cells against hypoxic damage during ITx. [Read the Full Post]

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

488 | Aug 28 2020

Zhaodong Wang et al.showed that EpSCs were used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering.Quercetin was a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1214 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

The Antitumor Efficiency of Zinc Finger Nuclease combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

511 | Aug 16 2020

Ci Ren et al. demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignances. [Read the Full Post]

Trichostatin A modulates the macrophage phenotype by enhancing autophagy to reduce inflammation during polymicrobial sepsis

506 | Aug 13 2020

Shu-Nan Cui et al. showed that TSA promoted the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improved the survival of mice with polymicrobial sepsis. [Read the Full Post]

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

682 | Aug 10 2020

Jingyu Deng et al. showed that Irisin played a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. [Read the Full Post]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes

685 | Aug 10 2020

Adrien Foca et al. emphasized that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies. [Read the Full Post]

EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets

497 | Aug 08 2020

Juraj Adamik et al. found that EZH2 exhibits complex roles in supporting osteoclast differentiation and function. [Read the Full Post]

Pentraxin-3 Mediates Prosurvival Actions of Interferon Tau in Bovine Luteinized Granulosa Cells

687 | Aug 06 2020

Raghavendra Basavaraja et al. suggested a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage. [Read the Full Post]

PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity

556 | Aug 03 2020

Hyungsoo Kim et al. provided a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response. [Read the Full Post]

In Vitro and In Vivo Efficacy of DNA Damage Repair Inhibitor Veliparib in Combination with Artesunate against Echinococcus granulosus

459 | Aug 02 2020

Y F Li et al. demonstrated that AS or AS in combination with Veliparib was effective for treating CE, especially the combination group. [Read the Full Post]

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer

583 | Aug 02 2020

Yifan Jiang et al. found that PARP inhibitors were an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer. [Read the Full Post]

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data

787 | Jul 28 2020

Mahdi Gharaibeh et al. showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. [Read the Full Post]

4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism

580 | Jul 18 2020

Weili Wang et al. provided a novel therapeutic strategy for MDS. [Read the Full Post]

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial

661 | Jul 17 2020

Andrew M Brunner et al. suggested that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. [Read the Full Post]

Protein Acetylation Derepresses Serotonin Synthesis to Potentiate Pancreatic Beta-Cell Function Through HDAC1-PKA-Tph1 Signaling

714 | Jul 13 2020

Yuqing Zhang et al. highlighted a novel role of HDAC1-PKA-Tph1 signaling in governing β-cell functional compensation by derepressing serotonin synthesis. [Read the Full Post]

In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- And Benzamide-Type Histone Deacetylase Inhibitors (HDACi)

774 | Jul 12 2020

Annabelle Friedrich et al. found that KSK64 revealed the highest genotoxic hazard and DDR stimulating potential, while TOK77 and MPK77 showed the lowest DNA damaging capacity. [Read the Full Post]

Histone Deacetylase Inhibition Prevents the Growth of Primary and Metastatic Osteosarcoma

1036 | Jul 07 2020

Jeremy J McGuire et al. provided rationale for clinical trials in osteosarcoma patients using the approved therapies panobinostat or romidepsin. [Read the Full Post]

Combination BET Family Protein and HDAC Inhibition Synergistically Elicits Chondrosarcoma Cell Apoptosis Through RAD51-Related DNA Damage Repair

881 | Jul 06 2020

Songwei Huan et al. disclosed that BET and HDAC inhibition synergistically inhibited cell growth and induced cell apoptosis through a mechanism that involved the suppression of RAD51-related HR DNA repair in chondrosarcoma cells. [Read the Full Post]

18 F-Fluoroestradiol ( 18 F-FES)-PET Imaging in a Phase II Trial of Vorinostat to Restore Endocrine Sensitivity in ER+/HER2- Metastatic Breast Cancer

812 | Jul 01 2020

Lanell M Peterson et al. found that Simultaneous HDACi and AI dosing in patients with cancers resistant to AI alone showed clinical benefit (6+ months without progression) in 4 of 10 evaluable patients. [Read the Full Post]

Imaging Assisted Evaluation of Antitumor Efficacy of a New Histone Deacetylase Inhibitor in the Castration-Resistant Prostate Cancer

750 | Jul 01 2020

Zude Chen et al. provided not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. [Read the Full Post]

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia

565 | Jun 28 2020

Mursal Sherzai et al. showed that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. [Read the Full Post]

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid

474 | Jun 24 2020

Mariah M Hoffman et al. indicated that 4SC-202 had both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and was an important potential cancer therapeutic to be investigated in vivo. [Read the Full Post]

EZH2 Is Involved in Vulnerability to Neuroinflammation and Depression-Like Behaviors Induced by Chronic Stress in Different Aged Mice

473 | Jun 23 2020

Wei Wang et al. found that EZH2 might be involved in susceptibility to neuroinflammation and depression-like behaviors in different aged mice. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

1225 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

504 | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

1219 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

Revealing the Selective Mechanisms of Inhibitors to PARP-1 and PARP-2 via Multiple Computational Methods

475 | Jun 17 2020

Hongye Hu et al. provided new insights about how inhibitors specifically bound to PARP-1 over PARP-2, which might help facilitate the design of highly selective PARP-1 inhibitors in the future. [Read the Full Post]

Mechanism and Current Progress of Poly ADP-ribose Polymerase (PARP) Inhibitors in the Treatment of Ovarian Cancer

0 | Jun 15 2020

Feiyue Zheng et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

822 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

Cell Cycle Arrest and Apoptosis Are Not Dependent on p53 Prior to p53-dependent Embryonic Stem Cell Differentiation

1251 | Jun 02 2020

Sushil K Jaiswal et al. found that the multiple roles of p53 in cell cycle regulation and apoptosis were first acquired during pluripotent stem cell differentiation. [Read the Full Post]

CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors

380 | Jun 01 2020

Emmanuel S Antonarakis et al. found that CDK12-altered prostate cancer was an aggressive subtype with poor outcomes to hormonal and taxane therapies as well as to PARP inhibitors. A proportion of these patients might respond favorably to PD-1 inhibitors, which implicated CDK12 deficiency in immunotherapy sensitivity. [Read the Full Post]

Small Molecule JQ1 Promotes Prostate Cancer Invasion via BET-independent Inactivation of FOXA1

523 | May 31 2020

Leiming Wang et al. indicated that JQ1 has an unexpected effect of promoting invasion in prostate cancer. [Read the Full Post]

PARP and PARG Inhibitors in Cancer Treatment

478 | May 28 2020

Dea Slade highlighted clinical performance of four PARP inhibitors used in cancer therapy (olaparib, rucaparib, niraparib, and talazoparib) and discussed the predictive biomarkers of inhibitor sensitivity, mechanisms of resistance as well as the means of overcoming them through combination therapy. [Read the Full Post]

Talazoparib in Patients With a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses From the Phase III EMBRACA Trial

522 | May 27 2020

Sara A Hurvitz et al. found that Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

733 | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase 2 study.

414 | May 15 2020

Lampert EJ et al. found that he PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Their correlative study results suggested immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination [Read the Full Post]

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay

388 | May 13 2020

Sirisena N et al. highlighted the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants. [Read the Full Post]

Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha

566 | May 10 2020

Koh MY et al. concluded that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors. [Read the Full Post]

Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination With Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma

510 | Apr 27 2020

Dan T Vogl et al. showed that at the recommended phase II dose of ricolinostat of 160 mg daily, the combination with bortezomib and dexamethasone is safe, well-tolerated, and active, suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy. [Read the Full Post]

The BET Bromodomain Inhibitor i-BET151 Impairs Ovarian Cancer Metastasis and Improves Antitumor Immunity

323 | Apr 15 2020

Ai Liu et al. showed that tumor metastasis may be suppressed by i-BET151 via the Stat3 pathway; this approach could be used as a strategy for the treatment of OC. [Read the Full Post]

Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC

316 | Apr 15 2020

Jonathan Welti et al. showed that BETi merit clinical evaluation as inhibitors of AR splicing and function, with trials demonstrating their blockade in proof-of-mechanism pharmacodynamic studies. [Read the Full Post]

OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models

319 | Apr 13 2020

Berenguer-Daizé C et al. demonstrated with OTX015 tumor levels 7 to 15-fold higher than in normal tissues, along with preferential binding of OTX015 to tumor tissue. The significant antitumor effects seen with OTX015 in GBM xenograft models highlight its therapeutic potential in GBM patients, alone or combined with conventional chemotherapies. [Read the Full Post]

Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance

686 | Apr 09 2020

Jane EP et al. provided new insights into mechanisms of treatment resistance in gliomas, hold promise for targeting recurrent disease, and provided a potential strategy for further exploration of next generation inhibitors. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

554 | Mar 30 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Bcl-2high mantle cell lymphoma cells are sensitized to acadesine with ABT-199

390 | Mar 23 2020

Montraveta A et al. supported the notions that antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and that the combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. [Read the Full Post]

Biguanides Induce Acute de novo Lipogenesis in Human Primary Sebocytes

385 | Mar 22 2020

Nicoll J et al. found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response. Biguanides did not activate AMPK in sebocytes, however, they significantly reduced oxygen consumption rate and increased lactate production. Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes. [Read the Full Post]

JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis

667 | Mar 19 2020

Heinicke U et al. indicated the second-generation HDACI JNJ-26481585 cooperates with chemotherapeutics to engage mitochondrial apoptosis in RMS cells, demonstrating that JNJ-26481585 represents a promising strategy for chemosensitization of RMS. [Read the Full Post]

The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction

578 | Mar 17 2020

He B et al. indicated that quisinostat, as a novel chemotherapy for HCC, exhibited excellent antitumor activity in vitro and vivo, which was even enhanced by the addition of sorafenib, implying combination of quisinostat with sorafenib a promising and alternative therapy for patients with advanced hepatocellular carcinoma. [Read the Full Post]

PXD101 significantly improves nuclear reprogramming and the in vitro developmental competence of porcine SCNT embryos

659 | Mar 12 2020

Jin JX et al. demonstrated that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming. [Read the Full Post]

Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

658 | Mar 11 2020

O'Connor OA et al. showed that monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication. [Read the Full Post]

MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model

1782 | Mar 08 2020

Huang HJ et al. revealed MGCD0103 could be a potential therapeutic agent against AD. [Read the Full Post]

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

601 | Mar 06 2020

Briere D et al. provided evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy. [Read the Full Post]

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

609 | Mar 03 2020

Marcos-Villar Let al. supported a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

529 | Feb 17 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

717 | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

438 | Feb 11 2020

Sun C found that MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. [Read the Full Post]

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

406 | Feb 10 2020

Wang H found that PARP trapping combined with specific pro-oxidative agents may provide safe and effective ways to broaden the therapeutic potential of PARP inhibitors. [Read the Full Post]

The histone deacetylase inhibitor romidepsin spares normal tissues while acting as an effective radiosensitiser in bladder tumours in vivo

599 | Feb 09 2020

Paillas S et al. demonstrated that romidepsin is an effective radiosensitiser in vitro and in vivo and does not increase the acute and late toxicity after ionising radiation. [Read the Full Post]

Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

617 | Feb 07 2020

Zhang AL et al. provided new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway

559 | Jan 31 2020

Zhang H et al. demonstrated that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provided preclinical proof-of-principle evidence for targeting EZH2 in patients with MB. [Read the Full Post]

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

543 | Jan 25 2020

Tremblay G et al. indicated that MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment. [Read the Full Post]

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells

510 | Jan 21 2020

Liu C et al. indicated that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation. [Read the Full Post]

Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer

795 | Jan 21 2020

Zheng F et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations

473 | Jan 20 2020

Jerez Y et al. discussed the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling. [Read the Full Post]

Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status

415 | Jan 20 2020

Venneker S et al. suggested that talazoparib combined with temozolomide or radiation are promising therapeutic strategies for chondrosarcoma, irrespective of IDH mutation status. A subset of chondrosarcomas may be deficient in nonclassical DNA repair pathways, suggesting that PARP inhibitor sensitivity is multifactorial in chondrosarcoma. [Read the Full Post]

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

712 | Jan 03 2020

Cao J et al. showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC. [Read the Full Post]

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

0 | Jan 01 2020

Wang YM et al. suggested that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment. [Read the Full Post]

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

621 | Jan 01 2020

Yang Y et al. indicated that FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI. [Read the Full Post]

Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

704 | Dec 31 2019

Chen X et al. suggested the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

0 | Dec 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia

614 | Dec 26 2019

Xia M et al. provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways. [Read the Full Post]

Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma

570 | Dec 18 2019

Di Martile M et al. indicated their study highlights the therapeutic potential of ITF2357, alone or in rational combination therapies, for bone and soft tissue sarcomas management. [Read the Full Post]

Histological effects of givinostat in boys with Duchenne muscular dystrophy

641 | Dec 16 2019

Bettica P et al. showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years. [Read the Full Post]

Reactive oxygen species generation and increase in mitochondrial copy number: new insight into the potential mechanism of cytotoxicity induced by aurora kinase inhibitor, AZD1152-HQPA

492 | Dec 13 2019

Zekri A et al. showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA. [Read the Full Post]

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

657 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

0 | Dec 08 2019

Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death

424 | Dec 01 2019

Tam EK et al. identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

0 | Dec 01 2019

Miranda TB et al. found that upon removal of DZNep, gene expression is reduced to its original state. This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

1392 | Nov 29 2019

Evanno E et al. showed that histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

0 | Nov 28 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Salidroside attenuates dextran sulfate sodium-induced colitis in mice via SIRT1/FoxOs signaling pathway

634 | Nov 22 2019

Li H et al. manifested that Sal may protect colitis mice by activating the SIRT1/FoxOs pathway, which is related to oxidative stress and apoptosis in colon tissues. [Read the Full Post]

Combinational therapeutic targeting of BRD4 and CDK7 synergistically induces anticancer effects in head and neck squamous cell carcinoma

311 | Nov 21 2019

Zhang W et al. revealed a novel therapeutic strategy of pharmacological inhibitions of BRD4 and CDK7 against HNSCC. [Read the Full Post]

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

693 | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

0 | Nov 11 2019

Ren Y et al. showed the Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

708 | Oct 24 2019

Yu Y et al. revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site. [Read the Full Post]

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis

761 | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels

403 | Oct 19 2019

Li N et al. indicated that dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer. [Read the Full Post]

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

650 | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts

540 | Oct 14 2019

Yuan AL et al. indicated that in laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ. [Read the Full Post]

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

608 | Oct 13 2019

Coleman RL et al. indicated that across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. [Read the Full Post]

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer

557 | Oct 11 2019

Noblejas-López MDM et al. provided options for further clinical development of these agents in TNBC. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

777 | Oct 11 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

829 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways

856 | Oct 05 2019

Wu Y et al. suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed. [Read the Full Post]

Entinostat for the treatment of breast cancer

760 | Sep 20 2019

Trapani D et a. offered the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines. [Read the Full Post]

Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma

732 | Sep 20 2019

Bayat Mokhtari R et al. indicated the significant reduction in initial tumorigenicity and subsequent abrogation upon serial xenografting suggests potential elimination of the NB CSC fraction. The significant potentiation of MS-275 by AZ is a promising therapeutic approach and one amenable for administration to patients given their current clinical utility. [Read the Full Post]

LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression

2074 | Sep 14 2019

Yao ZG et al. supports the role of HDAC inhibitors as a therapeutic strategy to target tumor angiogenesis. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

806 | Sep 09 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

762 | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

580 | Sep 08 2019

Yamamoto TM et al. demonstrated that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors. [Read the Full Post]

Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

519 | Sep 08 2019

Dockery LE et al. indicated this article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib's companion diagnostic test. [Read the Full Post]

Quantifying Risk Pathway Crosstalk Mediated by miRNA to Screen Precision drugs for Breast Cancer Patients

879 | Sep 03 2019

Xu Y et al. offers an effective way to screen precision drugs for various breast cancer subtype treatments. We also dissected the mechanism of optimal therapeutic drugs, which may provide novel insight into the precise treatment of cancer and promote researches on the mechanisms of action of drugs. [Read the Full Post]

Vorinostat-eluting poly(DL-lactide-co-glycolide) nanofiber-coated stent for inhibition of cholangiocarcinoma cells

841 | Sep 02 2019

Kwak TW et al. suggested the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment. [Read the Full Post]

Oncogenic enhancer of zeste homolog 2 is an actionable target in patients with non-small cell lung cancer

817 | Sep 02 2019

Shi B et al. showed that overexpression of EZH2 is a negative prognostic indicator. Increased EZH2 expression predicts for response to HDAC inhibitors and thus could serve as a biomarker for selecting NSCLC patients for treatment with HDAC inhibitors. [Read the Full Post]

PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer

477 | Aug 30 2019

Liu B et al. demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

0 | Aug 27 2019

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126in patients with MM may be warranted. [Read the Full Post]

Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

1939 | Aug 25 2019

He Y et al. revealed that ΔNp63 mediated anticancer effects of metformin and 4SC-202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC-202 treatment. Collectively, metformin and 4SC-202 synergistically promote intrinsic apoptosis through accelerating ubiquitin-mediated degradation of ΔNp63 in OSCC, and this co-treatment can serve as a potential therapeutic scheme for OSCC. [Read the Full Post]

Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma

547 | Aug 20 2019

Kurokawa C et al. showed that alisertibdisplays significant antitumor activity against primary GBM lines and xenografts, including patient derived GBM lines resistant to bevacizumab; these data support clinical translation in GBM. [Read the Full Post]

Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

580 | Aug 20 2019

Levesley J et al. indicated that selective small-molecule inhibitors of BCL-XL may enhance the efficacy of MLN8237 and other targeted chemotherapeutic agents. [Read the Full Post]

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma

659 | Aug 19 2019

Knutson SK et al. indicated these data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. [Read the Full Post]

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

684 | Aug 18 2019

Disney AJ et al. reported that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. [Read the Full Post]

PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation

635 | Aug 17 2019

Michmerhuizen AR et al. demonstrated that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT +/- PARPi in women with IBC [Read the Full Post]

Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review.

499 | Aug 17 2019

Boussios S et al. discussed multiple clinical trials that are underway examining the antitumor activity of such combination strategies. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

975 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Targeting autophagy potentiates the anti-tumor effect of PARP inhibitor in pediatric chronic myeloid leukemia

577 | Aug 07 2019

Liu Y et al. demonstrated that autophagy played a cyto-protective role in talazoparib-treated pediatric CML and co-treatment with talazoparib and autophagy inhibitor could induce synergetic anti-tumor effect, providing novel insights for pediatric CML treatment. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

0 | Jul 27 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma

375 | Jul 25 2019

Garcia PL et al. suggested that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. [Read the Full Post]

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

519 | Jul 22 2019

Belz JE et al. demonstrated that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. [Read the Full Post]

The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells

505 | Jul 14 2019

Arun B et al. indicated that the patients with BRCA1 allelic loss may also benefit from PARP inhibitor therapy if BRCA is further inhibited. [Read the Full Post]

BRCA1, PARP1 and γH2AX in acute myeloid leukemia: Role as biomarkers of response to the PARP inhibitor olaparib

1567 | Jul 14 2019

Faraoni I et al. showed the high sensitivity of AML blasts and the identification of biomarkers potentially able to predict response and/or resistance may foster further investigation of olaparib monotherapy for AML patients unfit to conventional chemotherapy. [Read the Full Post]

A patent review of arginine methyltransferase inhibitors (2010-2018)

732 | Jul 10 2019

Li X et al. summarized the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

877 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers

768 | Jul 03 2019

Katoh M indicated that SMO inhibitors can remodel the immunosuppressive TME that is dominated by M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells and regulatory T cells, and thus, a Phase I/II clinical trial of the immune checkpoint inhibitor pembrolizumab with or without vismodegib in BCC patients is ongoing. [Read the Full Post]

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells

705 | Jun 26 2019

Cao YP et al. demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested. [Read the Full Post]

Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells

893 | Jun 23 2019

Nashine S et al. revealed that AMD mitochondria regulate epigenetic mechanisms i.e., methylation and acetylation status. Demethylation using 5-Aza-2'-deoxycytidine (DAC) caused differential expression of VEGF-A gene in AMD cells. Trichostatin A (TSA), an HDAC inhibitor, also influenced protein levels of VEGF-A, HIF1α, NFκB, and CFH in AMD cells. This study might advance the field of AMD research since in addition to highlighting the critical role of nuclear-mitochondrial interactions that influence epigenetic mechanisms in AMD patients, this work suggests epigenetic profiles as potential therapeutic targets for AMD. [Read the Full Post]

BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation

755 | Jun 22 2019

Li YL et al. found that BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy. [Read the Full Post]

Reciprocal Relationship Between HDAC2 and P-Glycoprotein/MRP-1 and Their Role in Steroid Resistance in Childhood Nephrotic Syndrome

732 | Jun 22 2019

Singh H et al. found that reduced HDAC2 and increased P-gp/MRP-1 activity may play a role in response to steroids in childhood NS. HDAC2 and P-gp/MRP-1 are in reciprocal relationship with each other. [Read the Full Post]

Histone deacetylase 6 inhibitor ACY-1215 protects against experimental acute liver failure by regulating the TLR4-MAPK/NF-κB pathway

2241 | Jun 19 2019

Zhang WB et al. showed that ACY-1215 has potential therapeutic value in mice with ALF by directly inhibiting inflammatory response via regulation of the TLR4-MAPK/NF-kB pathway. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

718 | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

709 | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

594 | May 27 2019

Zekri A et al. showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. [Read the Full Post]

Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive acute myeloid leukemia

808 | May 25 2019

Luskin MR et al. indicated that expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

808 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition

507 | May 19 2019

Gabbasov R et al. suggested that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents. [Read the Full Post]

Hydroxysafflor yellow A inhibited lipopolysaccharide-induced non-small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

437 | May 18 2019

HYSA suppressed LPS-mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation-mediated NSCLC. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

892 | May 09 2019

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

689 | May 07 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Thromboembolic events in polycythemia vera

1066 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

1176 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

2619 | Apr 21 2019

Lim RR et al. concludd that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. [Read the Full Post]

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer

928 | Apr 14 2019

Kirschner AN et al. showed that PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation. [Read the Full Post]

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

874 | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

545 | Apr 09 2019

Moore KN et al. identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. [Read the Full Post]

Roxadustat in the treatment of anaemia in chronic kidney disease

794 | Mar 31 2019

Del Vecchio L et al showed that Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies. [Read the Full Post]

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China

776 | Mar 31 2019

Chen N et al. showed that FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program. [Read the Full Post]

MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer

639 | Mar 29 2019

Yi J et al. show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

859 | Mar 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

688 | Mar 28 2019

Lux S et al. showed that acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

777 | Mar 24 2019

Ren Y et al. indicated that the Sirt1 activator, SRT1720, exerts protective effects against UUO-induced tubulointerstitial fibrosis. The mechanisms of action of SRT1720 may include, at least in part, the suppression of renal oxidative stress and the TGF-β1/CTGF signalling pathway. The Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury

816 | Mar 12 2019

Schmitt HM et al. showed the inhibition of HDAC3 activity with systemic dosing of RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss after acute optic nerve injury. [Read the Full Post]

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

552 | Mar 11 2019

Wang YM et al. suggested that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment. [Read the Full Post]

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

988 | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway

515 | Mar 08 2019

Zhao X et al. demonstrated that compound C inhibited the phosphorylation of JNK and its target c-Jun. Blocking JNK by SP600125 or siRNA suppressed autophagy induction upon compound C treatment. Moreover, compound C induced p38 MAPK activation, and its inhibition promoted autophagy induction via JNK activation. In addition, compound C induced p53 expression, and its inhibition attenuated compound C-induced autophagic response. Thus, compound C triggers autophagy, at least in part, via the JNK and p53 pathways in human CCA cells. In conclusion, suppresses autophagy could increase compound C sensitivity in human CCA. [Read the Full Post]

In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors

544 | Mar 07 2019

Hao J et al. demonstrated the potential of zebrafish as an attractive complementary platform for drug development that incorporates an assessment of in vivo bioactivity and selectivity in the context of a living organism. [Read the Full Post]

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

932 | Mar 06 2019

Bao B et al. indicated that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. [Read the Full Post]

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients

756 | Mar 03 2019

Tedesco-Silva H et al. indicated that sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

960 | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes

420 | Feb 26 2019

Aury-Landas J et al. showed DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

543 | Feb 26 2019

Miranda TB et al. suggested that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

695 | Feb 18 2019

Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]

PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia

435 | Feb 08 2019

Guo H et al. found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia. [Read the Full Post]

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

826 | Feb 07 2019

Martin MJ et al. supported a model in which the combination of osimertinib and OxPhos inhibitors can delay or prevent resistance in osimertinib-naïve tumour cells, and represents a novel strategy that warrants further pre-clinical investigation. [Read the Full Post]

Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism

2573 | Jan 11 2019

Stammler D et al. indicated that in addition to the conventional inflammasome-dependent IL-1β cleavage pathway, dendritic cells and macrophages are capable of generating, secreting, and processing bioactive IL-1β by a novel, caspase-8-dependent mechanism. [Read the Full Post]

Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

881 | Jan 09 2019

Yang X et al. demonstrated that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

0 | Jan 07 2019

Valdez BC et al. further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity

2072 | Jan 03 2019

Borriello F et al. provided insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity. [Read the Full Post]

Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

736 | Jan 02 2019

Bernasconi E et al. indicated the use of combination schemes targeting EZH2, mTOR and BTK alongside BET bromodomains. [Read the Full Post]

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

762 | Jan 02 2019

Parasramka M et al. showed that NEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies. [Read the Full Post]

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification

746 | Dec 31 2018

Gherardi S et al. suggested therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

1257 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Enhanced efficacy of 5-fluorouracil in combination with a dual histone deacetylase and phosphatidylinositide 3-kinase inhibitor (CUDC-907) in colorectal cancer cells

1188 | Dec 26 2018

Hamam R et al. revealed, for the first time, the enhanced inhibitory effect of CUDC-907 against CRC cells when combined with 5-FU, supporting the application of this combination as a potential therapeutic strategy in CRC treatment. [Read the Full Post]

CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle

1354 | Dec 26 2018

Ali D et al. revealed that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation. [Read the Full Post]

Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

455 | Dec 25 2018

Eyer L et al. indicated that high antiviral activity and low cytotoxicity of C2' methylated or C4' azido substituted pharmacophores suggest that such compounds might represent promising candidates for further development of potential therapeutic agents in treating TBEV infection. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

955 | Dec 20 2018

Valdez BC et al. further implied the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

768 | Dec 15 2018

Chhajer R et al. identified an Aurora kinase homolog in L. donovani implicated in cell-cycle progression, whose inhibition led to aberrant changes in cell-cycle progression and reduced viability. [Read the Full Post]

Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute lymphoblastic leukemia

797 | Dec 13 2018

Spartà AM et al. indicated that PLK1 and AK inhibitors display the potential for being employed in innovative therapeutic strategies for improving T-ALL patient outcome. [Read the Full Post]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

1490 | Dec 09 2018

Zhang M et al. indicated that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system. [Read the Full Post]

Regulatory Mechanisms Underlying the Expression of Prolactin Receptor in Chicken Granulosa Cells

572 | Dec 08 2018

Hu S et al. provided new insights into the regulatory mechanisms controlling the expression of PRLR in granulosa cells. [Read the Full Post]

PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage

2052 | Dec 05 2018

Chen T et al. indicated that PARP inhibition through PJ34 might be an important therapeutic drug for SAH. [Read the Full Post]

AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells

686 | Dec 04 2018

Zhang TG et al. showed that AMPK activator acadesine (AICAR) alleviated INH-caused impairment of mitochondrial biogenesis by activation of silent information regulator two ortholog 1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC1 α) pathway in HepG2 cells. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

1322 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

5968 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

0 | Nov 20 2018

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo

1962 | Nov 19 2018

Zhu Y et al. indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC. [Read the Full Post]

Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued transcription of HIF-1α in human umbilical vein endothelial cells

1951 | Nov 19 2018

Zhu J et al. suggested that oxytocin receptor signaling promoted the angiogenic behaviors of HUVECs via Gli1-indcued transcription of HIF-1α. We provided novel molecular insights into endothelial cell-mediated angiogenesis. [Read the Full Post]

Epigenetic drug combination induces remission in mouse xenograft models of pediatric acute myeloid leukemia

1040 | Nov 18 2018

Gopalakrishnapillai A et al. indicated the expression of mutant p53 in MV4;11 cells reduced sensitivity to azacitidine-panobinostat combination, suggesting that p53 may be a predictor of response to epigenetic therapy in pediatric AML. [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

1199 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

1398 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Effects of the histone deacetylase inhibitor 'Scriptaid' on the developmental competence of mouse embryos generated through round spermatid injection

1088 | Nov 11 2018

Kong P et al. supported through grants from the National Key Research Program of China (No. 2016YFC1304800); the National Natural Science Foundation of China (Nos: 81170756, 81571486); the Natural Science Foundation of Shanghai (Nos: 15140901700, 15ZR1424900) and the Programme for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. There are no conflicts of interest to declare. [Read the Full Post]

Curcumin and its cyclohexanone analogue inhibited human Equilibrative nucleoside transporter 1 (ENT1) in pancreatic cancer cells

1939 | Nov 08 2018

Revalde JL et al. concluded that curcumin and A13 are inhibitors of the ENT1 transporter, but only at high concentrations (2-20µM). [Read the Full Post]

Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

1040 | Nov 03 2018

Yuan J et al. suggested that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1616 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

952 | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

966 | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4

693 | Oct 06 2018

Castex J et al. showed that by repression of Sirt4, Lsd1 directs the epigenetic control of TSC immortality via maintenance of metabolic flexibility. [Read the Full Post]

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

0 | Oct 04 2018

Grandy RA et al. established a new dimension of chromatin regulation important in the maintenance of pluripotency. [Read the Full Post]

CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency

1001 | Sep 18 2018

Wang XQ et al. demonstrated an essential role for the CDK1-PDK1-PI3K/Akt kinase signaling pathway in the regulation of self-renewal, differentiation, and somatic reprogramming, which provides a novel kinase cascade mechanism for pluripotency control and acquisition. [Read the Full Post]

P-TEFb Kinase Activity Is Essential for Global Transcription, Resumption of Meiosis and Embryonic Genome Activation in Pig

987 | Sep 18 2018

Oqani RK et al. suggested that P-TEFb kinase activity is crucial for oocyte maturation, embryo development and regulation of RNA transcription in pig. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

1352 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Sep 03 2018

Pu Y et al. suggested that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

1553 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human

972 | Aug 18 2018

Jia L et al. illustrated a potential translational research bridging animal models and human studies. [Read the Full Post]

Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage

0 | Aug 08 2018

Vienken H et al. showed that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

0 | Aug 08 2018

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

1343 | Aug 05 2018

Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

1114 | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

1592 | Aug 02 2018

Zhang M et al. demonstrated for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy. [Read the Full Post]

HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

1278 | Aug 01 2018

Wang Z et al. suggested that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma. [Read the Full Post]

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

4179 | Jul 31 2018

Yu J et al. suggested that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells. [Read the Full Post]

The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3

1216 | Jul 31 2018

Ni L et al. showed that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. [Read the Full Post]

GSK621 Targets Glioma Cells via Activating AMP-Activated Protein Kinase Signalings

779 | Jul 26 2018

Jiang H et al. summarized that GSK621 inhibits human glioma cells possibly via activating AMPK signaling. This novel AMPK activator could be a novel and promising anti-glioma cell agent. [Read the Full Post]

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

945 | Jul 25 2018

Yang T et al. indicated that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. [Read the Full Post]

Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

880 | Jul 24 2018

Wang GF et al. identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases. [Read the Full Post]

Downregulation of the PHLDA1 gene in IMR-32 neuroblastoma cells increases levels of Aurora A, TRKB and affects proteins involved in apoptosis and autophagy pathways

904 | Jul 24 2018

Durbas M et al. showed possible links of the protein to regulation of features of mitochondria and formation of autophagosomes. [Read the Full Post]

The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia

1210 | Jul 22 2018

Rauzan M et al. demonstrated that SB939 overcomes BIM deletion polymorphism-induced TKI resistance, and suggest that SB939 may be useful in treating CML patients with BIM deletion-associated TKI resistance. [Read the Full Post]

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

1211 | Jul 22 2018

Dai Y et al. identified clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jul 20 2018

Laporte AN, et al. indicated this assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

1602 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway

3233 | Jul 04 2018

Deng H, et al. indicated RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

4450 | Jul 03 2018

Gu S et al. demonstrated that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Jul 03 2018

Meng Z, et al. indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Small molecule epigenetic screen identifies novel EZH2 and HDAC inhibitors that target glioblastoma brain tumor-initiating cells

648 | Jun 30 2018

Grinshtein N et al. identified key epigenetic modulators in GBM that regulate BTIC growth and survival and highlight promising combination therapies. [Read the Full Post]

Therapeutic effects of histone deacetylase inhibitors in a murine asthma model

1240 | Jun 28 2018

Ren Y, et al. suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice. [Read the Full Post]

LTR12 promoter activation in a broad range of human tumor cells by HDAC inhibition

1308 | Jun 28 2018

Krönung SK et al. showed that inhibition of HDAC1-3 is sufficient for LTR12 activation. Importantly, HDAC inhibitors induce LTR12 activity not only in testicular cancer cells, but also in cells derived from many additional tumor species. Finally, we characterize the transcription factor NF-Y as a mediator of LTR12 promoter activity and HDAC inhibitor-induced apoptosis, in the context of widespread genomic binding of NF-Y to specific LTR12 sequences. Thus, HDAC inhibitor-driven LTR12 activation represents a generally applicable means to induce proapoptotic genes in human cancer cells. [Read the Full Post]

HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer

1315 | Jun 27 2018

Li A et al. indicated that HDAC5 is a promising prognostic marker and drug target for BC and that the combination of LMK-235 and bortezomib presents a novel therapeutic strategy for BC. [Read the Full Post]

HPOB, an HDAC6 inhibitor, attenuates corticosterone-induced injury in rat adrenal pheochromocytoma PC12 cells by inhibiting mitochondrial GR translocation and the intrinsic apoptosis pathway

1104 | Jun 26 2018

Li ZY et al. suggested that the anti-apoptotic activity of HDAC6 inhibition against the mitochondria-mediated impairment pathway might be mechanistically linked to the hyperacetylation of Hsps and consequent suppression of GR translocation to the mitochondria. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein-and-Sensitizes-the-Mitochondrial-Apoptotic-Pathway

1478 | Jun 23 2018

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jun 21 2018

Laporte AN et al. reported use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells

1359 | Jun 15 2018

Wang Z et al. explained the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. [Read the Full Post]

Human Papillomavirus Downregulates the Expression of IFITM1 and RIPK3 to Escape from IFNγ- and TNFα-Mediated Antiproliferative Effects and Necroptosis

1820 | Jun 12 2018

Ma W et al. revealed how hrHPV deregulates two pathways involved in cell death and growth regulation to withstand immune-mediated control of hrHPV-infected cells. [Read the Full Post]

Impairment of hypoxia-induced HIF-1α signaling in keratinocytes and fibroblasts by sulfur mustard is counteracted by a selective PHD-2 inhibitor

3102 | Jun 10 2018

Deppe J, et al. described a pathomechanism by which SM negatively affects hypoxia-stimulated HIF-1α signaling in keratinocytes and fibroblasts and thus possibly contributes to delayed wound healing in SM-injured patients that could be treated with PHD-2 inhibitors. [Read the Full Post]

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

2442 | Jun 10 2018

Szczepanowicz K et al. indicated the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity. [Read the Full Post]

Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation

734 | Jun 09 2018

McCullough CE et al. pointed to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys-274 autoacetylation for subsequent cognate substrate acetylation. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

0 | Jun 07 2018

Hu L et al. indicated that IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins

1055 | Jun 01 2018

Li R et al. provided evidence for an anti-proliferative role of Ulk1 in response to Hsp90 inhibition in cancer cells. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | May 12 2018

Yun T et al. found that HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta

1989 | May 08 2018

Zuo R et al. found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. [Read the Full Post]

Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation

1231 | May 06 2018

Wang M et al. illustrated two divergent pathways mediating a continuous increase of DNA methylation and also sheds further light on the epigenetic basis for single-cell differentiation in plants. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1799 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1

892 | Apr 20 2018

Zhang Z et al. provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3296 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice

1240 | Apr 04 2018

Sun Q et al. suggested that fisetin has a therapeutical potential for treating ALD. [Read the Full Post]

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition

1857 | Apr 03 2018

Tse AK et al. illustrated a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

0 | Mar 30 2018

Tang X et al. demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. [Read the Full Post]

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation

1440 | Mar 24 2018

van de Ven AL et al. suggested that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCAmutations, such as those with PTEN and TP53 deletions. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

2083 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1742 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

1597 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells

1307 | Mar 14 2018

Park JY et al. indicated the Epac-Rap1-Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

0 | Mar 10 2018

Wasim L et al. suggest a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression

1731 | Mar 10 2018

Terranova-Barberio M et al. suggested that the combination of HDACi (e.g., VPA) and capecitabine is an innovative antitumor strategy that warrants further clinical evaluation for the treatment of metastatic breast cancer. [Read the Full Post]

Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines

1483 | Feb 14 2018

Jane EP et al. provided a new insight into the link between Bcl-xL and survivin inhibition for the development of novel therapies for glioma. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

3534 | Feb 14 2018

You M et al. provided molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

Reprogramming of histone methylation controls the differentiation of monocytes into macrophages

793 | Feb 13 2018

Zheng QF et al. elucidated mechanisms crucial to the dynamic establishment of epigenetic memory, which is central to the maintenance of the MP differentiation blockade. [Read the Full Post]

Fibroblast Growth Factor 21 (FGF21) Promotes Formation of Aerobic Myofibers via the FGF21-SIRT1-AMPK-PGC1α Pathway

828 | Feb 07 2018

Liu X et al. revealed a novel mechanism of myogenesis and muscle fiber transformation and indicated that FGF21 serves as a vital regulator of muscle development and important contributor to the pathogenesis of myopathy. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

3204 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

830 | Feb 05 2018

Grandy RA et al. established a new dimension of chromatin regulation important in the maintenance of pluripotency. [Read the Full Post]

Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney

777 | Feb 04 2018

Cai M et al. concluded that glucose is a potent inducer of histone acetylation and methylation, which in turn leads to upregulation of OPN gene expression. Treatment targeting histone marks may therefore represent an alternative method to protect kidneys from deleterious effects of glucose. [Read the Full Post]

A novel HDAC6 inhibitor Tubastatin A: Controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses Temozolomide-induced ER stress-tolerance in GBM cells

1965 | Jan 27 2018

Li ZY et al. showed that the balance of HDAC6-p97/VCP was crucial to ERST-associated TMZ resistance and that HDAC6 inhibition might be a synergistic target and strategy along with TMZ for the improvement of clinical glioma treatment. [Read the Full Post]

Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma

1283 | Jan 16 2018

Liu F et al. provided a solid evidence for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC. [Read the Full Post]

CK1δ kinase activity is modulated by protein kinase C α (PKCα)-mediated site-specific phosphorylation

3798 | Jan 14 2018

Meng Z et al. contributed to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. [Read the Full Post]

Concomitant BET and MAPK blockade for effective treatment of ovarian cancer

838 | Jan 08 2018

Jing Y et al. supportted concomitant BET and MAPK blockade as an effective therapeutic strategy in ovarian cancer. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | Jan 03 2018

Yun T et al. induced p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

3233 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways

1799 | Dec 26 2017

Ni L et al. provided a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan. [Read the Full Post]

G-quadruplex-based fluorometric biosensor for label-free and homogenous detection of protein acetylation-related enzymes activities

1274 | Dec 26 2017

The potency of this assay is further demonstrated by detecting HAT/HDAC activity in cell lysates and evaluating HAT and HDAC-targeted inhibitors, C464 and EX 527, respectively. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

1983 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1

1961 | Dec 23 2017

Wang L et al. found the potential clinical significance, as a large proportion of patients could be at risk of developing severe toxicity if irinotecan is co-administered with belinostat. [Read the Full Post]

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL

1694 | Dec 19 2017

Hasanov E et al. identified VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. [Read the Full Post]

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

1332 | Dec 11 2017

Maimaiti Y, et al. indicated that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer. [Read the Full Post]

Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

1492 | Dec 02 2017

Peters TL et al. characterized recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. [Read the Full Post]

The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb

967 | Nov 27 2017

Lu P et al. suggested that the BET inhibitor OTX015 may be a candidate for anti-HIV-1-latency therapies. [Read the Full Post]

Kinome Profiling Identifies Druggable Targets for Novel Human Cytomegalovirus (HCMV) Antivirals

898 | Nov 26 2017

Arend KC et al. showed the utility of MIB-MS kinome profiling for identifying existing kinase inhibitors that can potentially be repurposed as novel antiviral drugs. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

2007 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

Targeting protein kinase C in mantle cell lymphoma

1564 | Nov 16 2017

Rauert-Wunderlich H et al. showed that MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

1050 | Nov 12 2017

Tang X et al. demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. [Read the Full Post]

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

2239 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

905 | Nov 04 2017

Chen D et al. suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

0 | Oct 29 2017

Noguchi K et al. suggested that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

1325 | Oct 28 2017

Yalon M et al. showed that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. [Read the Full Post]

ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli

1702 | Oct 22 2017

Siddharth S et al. showed that increased APC physically interacts with PARP-1 and inhibits PARylation causing the non assembly of base excision repair (BER) multiprotein complex, resulting in an irreparable DNA damage and subsequent apoptosis. Knockdown of APC in mBCSCs inhibited DNA damage, increased BER and PARylation, reduces apoptosis while the over-expression of APC in BT20 (APC low expressing) cells reversed the effect. Thus, combination of QC and ABT-888 decreased mBCSCs growth by activating APC and inhibiting BER within the cells. [Read the Full Post]

Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer

1733 | Oct 20 2017

Cardillo TM et al. demonstrated the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

0 | Oct 11 2017

Chang X et al. reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

4211 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

0 | Oct 09 2017

Eyer L, et al. suggested that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

0 | Oct 09 2017

Eyer L, et al. suggested that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

0 | Oct 06 2017

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

Inhibition of Extracellular Calcium Influx Results in Enhanced IL-12 Production in LPS-Treated Murine Macrophages by Downregulation of the CaMKKβ-AMPK-SIRT1 Signaling Pathway

1371 | Oct 05 2017

Liu X et al. demonstrated a new role of transmembrane calcium mobilization in immunity modulation such that inhibition of calcium influx leads to impaired activation of CaMKKβ-AMPK-SIRT1 signaling pathway which lifts restriction on NF-κB activation and results in enhanced IL-12 production. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Mohseni J et al. established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines.

1834 | Sep 17 2017

Pinkerneil M et al. combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

0 | Sep 16 2017

Mohseni J et al. showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Inhibition of PRMT5 suppresses osteoclast differentiation and partially protects against ovariectomy-induced bone loss through downregulation of CXCL10 and RSAD2

865 | Aug 29 2017

Dong Y et al. found that PRMT5 is an activator of osteoclast differentiation and inhibition of PRMT5 partially suppressed osteoclastogenesis through downregulation of CXCL10 and RSAD2. [Read the Full Post]

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

1286 | Aug 28 2017

Li Q et al. revealed that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). [Read the Full Post]

Leptin-STAT3-G9a Signaling Promotes Obesity-Mediated Breast Cancer Progression

1051 | Aug 28 2017

Chang CC et al. showed how targeting STAT3-G9a signaling regulates CSC plasticity during obesity-related breast cancer progression, suggesting a novel therapeutic paradigm to suppress CSC pools and limit breast malignancy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

2008 | Aug 27 2017

Laporte AN et al. report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

Brain-Penetrating Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 in vitro

1969 | Aug 24 2017

Lauren Green found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer. [Read the Full Post]

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration

2056 | Aug 23 2017

Xu Y et al. found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

2413 | Aug 23 2017

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

2433 | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

2684 | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

873 | Aug 08 2017

Han T et al. suggested that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

1735 | Jul 31 2017

Noguchi K et al. suggests that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

1550 | Jul 30 2017

Katsha A et al. indicated that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA-EIF4E-c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways.

0 | Jul 29 2017

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways.

0 | Jul 22 2017

Ghosh R et al. highlighted specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

2157 | Jul 20 2017

Wasim L et al. suggested a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Histone deacetylase inhibitor panobinostat induces calcineurin degradation in multiple myeloma

2427 | Jul 19 2017

Imai Y et al. findings underscore the usefulness of calcineurin-targeted therapy in MM patients, including patients who are resistant to bortezomib. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

2573 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

0 | Jul 07 2017

Buoncervello M et al. opened a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

2402 | Jun 26 2017

Nunn AD et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5869 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

2247 | Jun 12 2017

Bi G et al. found that PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

3584 | Jun 11 2017

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells

1785 | Jun 10 2017

Vanden Heuvel JP et al. found that cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. [Read the Full Post]

The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line

1982 | Jun 02 2017

Wang J et al. found that serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

The Promoting Effect of Radiation on Glucose Metabolism in Breast Cancer Cells under the Treatment of Cobalt Chloride

2058 | May 27 2017

Zhao CB et al. found that the combination of radiation and hypoxia could promote the glucose metabolism. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2924 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3

0 | May 24 2017

Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

0 | May 23 2017

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2765 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

0 | May 12 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 10 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.

0 | May 10 2017

Those results improve Li Det al.'s understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 09 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1919 | May 02 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

0 | May 01 2017

de Andrade PV et al demonstrate that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

3485 | Apr 30 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1855 | Apr 25 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

1610 | Apr 22 2017

Lakatos P et al. found that PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2782 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

0 | Apr 06 2017

Hsu YC et al showed that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. [Read the Full Post]

Activation of the miR-34a/SIRT1/p53 Signaling Pathway Contributes to the Progress of Liver Fibrosis via Inducing Apoptosis in Hepatocytes but Not in HSCs

1718 | Apr 04 2017

Tian XF et al. found that the miR-34a/SIRT1/p53 signaling pathway might be a promising therapeutic target for liver fibrosis. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Mar 23 2017

Meng Z et al indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2650 | Mar 14 2017

Tsunoda K et al. suggested that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

3484 | Mar 13 2017

Fang M et al revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

0 | Feb 28 2017

Ma HT, et al.'s results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeuticmediated cell death

1860 | Feb 27 2017

Chen H, et al.'s results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

0 | Feb 17 2017

When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. [Read the Full Post]

NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

1186 | Feb 13 2017

Hu P, et al.‘s ’ study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

0 | Feb 12 2017

Jian Y, et al.'s study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1482 | Feb 02 2017

These evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways

1442 | Feb 02 2017

Guan JH et al. revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

3319 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

2945 | Jan 27 2017

Meng Z et al. found that non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2847 | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death

2011 | Jan 15 2017

Chen H et al. found the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

2075 | Jan 15 2017

Ma HT et al. provided a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2887 | Jan 05 2017

Jian Y, et al.'s our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

1461 | Jan 05 2017

Hu P, et al.‘'s study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

1416 | Dec 29 2016

The study of Guan JH, et al. primarily revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1630 | Dec 28 2016

Zhang W, et al.'s evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

2566 | Dec 27 2016

The results of Nunn AD, et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

2939 | Dec 22 2016

The findings of Buoncervello M et al. open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways

2225 | Dec 14 2016

Ghosh R et al.'s findings highlight specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients.

0 | Nov 29 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J, et al have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines

2858 | Nov 28 2016

Specific pharmacological inhibition of class I HDACs by 4SC-202 impairs UC cell viability, inducing cell cycle disturbances and cell death. Combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

4129 | Nov 25 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J et al showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

2986 | Nov 24 2016

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

2202 | Nov 23 2016

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

1455 | Nov 20 2016

Antiviral activity was identified when 2'-C-methylated nucleosides were tested, suggesting that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

2085 | Nov 17 2016

Chang X et al. revealed that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

2084 | Nov 11 2016

Yalon M et al. found that drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.

2855 | Nov 08 2016

Davis MR, et al. found that The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. [Read the Full Post]

Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines

2282 | Nov 02 2016

Hegde M et al. revealed that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity. [Read the Full Post]

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests

2885 | Oct 31 2016

Shinde V, et al. found that the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. [Read the Full Post]

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

2933 | Oct 28 2016

[Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

5721 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3'-monoxime

2478 | Oct 21 2016

Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

3118 | Oct 20 2016

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3

3189 | Oct 09 2016

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer

2754 | Oct 09 2016

Li D et al. improved the understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

2819 | Sep 28 2016

De Andrade PV et al demonstrated that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

No Significant Cytotoxic Effect of the EZH2 Inhibitor Tazemetostat on Pediatric Glioma Cells with Wildtype Histone 3 or Mutated Histone 3.3

1330 | Sep 18 2016

Wiese M et al. suggested that EZH2 inhibition might not offer an effective single agent treatment option for paedHGG patients. However, the therapeutic efficacy in combination with cytotoxic and/or other epigenetically active agents still has to be elucidated. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2312 | Sep 09 2016

Hsu YC et al. identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. [Read the Full Post]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

5138 | Sep 02 2016

Fang M, et al. revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

The interferon-related developmental regulator 1 is a key factor for human papillomavirus-induced NFкB inhibition

5157 | Mar 24 2015

Tummers et al. found hrHPV impairs immune response by inhibiting the acetylation of NFкB/RelA K310 in keratinocytes. [Read the Full Post]

Bromodomain and extra-terminal proteins are required in STAT5-mediated transcription

5524 | Mar 23 2015

Pinz et al. found deacetylase inhibitors lead to the delocalization of the bromodomain and extra-terminal (BET) protein Brd2, as well as Brd2-related factor TBP to hyperacetylated chromatin, via the global upregulation of histone acetylation. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

9772 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Histone deacetylase inhibitors have negative effects on the elimination of HIV-infected cells by cytotoxic T-Lymphocytes

5207 | Mar 02 2015

Jones et al. tested the impact of three HDACis, suberanilohydroxamic acid (SAHA), romidepsin and panobinostat, in clinical development on immune effectors functions, such as T-cell effector. [Read the Full Post]

An inverse correlation between homologous recombination and Polθ in epithelial ovarian cancers

4309 | Feb 27 2015

Ceccaldi et al. reported that HR activity inversely correlated with Polθ expression in EOCs. [Read the Full Post]

The combination of broadly neutralizing antibodies and viral inducers can suppress the establishment of HIV-1 latent reservoir

6516 | Feb 13 2015

Halper-Stromerg et al. demonstrated that broadly neutralizing antibodies (bNAbs) can suppress the establishment of a silent reservoir in humanized mice. [Read the Full Post]

Star27 overcomes synthetic lethal toxicity for FLT3-targeted therapy against acute myeloid leukemia

4908 | Feb 06 2015

For overcoming myelosuppression, Warkentin et al. reported a staurosporine analog, Star27, that enable to inhibit FLT3 while avoiding KIT inhibition. [Read the Full Post]

Recently identified CHEK2 Y390C mutation facilitates early breast cancer development

6775 | Feb 05 2015

Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. [Read the Full Post]

The distribution of primary cilia in the mouse embyo

4979 | Jan 27 2015

Bangs et al. demonstrate the time and location that primary cilia appear in the mouse embryo. [Read the Full Post]