Proteases

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]

PR-957 retards rheumatoid arthritis progression and inflammation by inhibiting LMP7-mediated CD4+ T cell imbalance

38 | Jan 21 2024

PR-957 demonstrates potential in alleviating rheumatoid arthritis by targeting LMP7-mediated CD4+ T cell imbalances, offering a promising avenue for therapeutic intervention. [Read the Full Post]

Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer's Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13

14 | Jan 15 2024

This study suggests that astaxanthin may offer promise in mitigating Alzheimer's disease-related cognitive and biochemical changes in zebrafish by inhibiting MMP-13 activity, potentially indicating a multi-targeted therapeutic approach for AD management. [Read the Full Post]

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

57 | 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]

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]

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]

Vascular smooth muscle cell mechanotransduction through serum and glucocorticoid inducible kinase-1 promotes interleukin-6 production and macrophage accumulation in murine hypertension

33 | Dec 27 2023

The investigation demonstrated that mechanical activation of serum and glucocorticoid-inducible kinase-1 (SGK-1) in aortic vascular smooth muscle cells (VSMCs), both in vivo in hypertensive mice and in vitro through cyclic stretch, promotes inflammatory signaling and macrophage accumulation, suggesting SGK-1 as a potential pharmacotherapeutic target for hypertensive vascular pathology. [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]

In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma

57 | Dec 19 2023

The study demonstrates the potential therapeutic efficacy of the gamma-secretase inhibitor MK0752 in head and neck squamous cell carcinoma, particularly inducing apoptosis in human-papillomavirus-positive tumors, suggesting its viability as a targeted treatment option pending further validation and mechanistic exploration. [Read the Full Post]

Structure-Based Lead Optimization of Enterovirus D68 2A Protease Inhibitors

34 | Dec 13 2023

In this study, researchers elucidated the X-ray crystal structures of EV-D68 2Apro and its C107A mutant, utilized molecular dynamics simulations to predict the binding pose of telaprevir, and optimized its structure, leading to the discovery of potent 2Apro inhibitors with improved antiviral activity against Enterovirus D68. [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]

Natto extract inhibits infection caused by the Aujeszky

22 | Dec 05 2023

The discovery that Fraction No. 10 from natto, a traditional Japanese fermented food, can functionally impair Aujeszky's disease virus (ADV) infection through serine protease inhibition, providing a potential avenue for developing natural antiviral treatments in the swine industry, holds significant promise for mitigating economic losses and promoting animal welfare. [Read the Full Post]

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies

20 | Dec 04 2023

The study identified delanzomib and tibalosin as potential allosteric inhibitors of TrkA through molecular docking and dynamics simulations, offering promising candidates for experimental evaluation in cancer therapy due to their stable interactions and high binding affinities. [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]

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African medicines agency

75 | Nov 30 2023

The study highlights the foundational role of regional medicines regulatory harmonization programs, such as the African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation (EAC-MRH) initiatives, in supporting the operationalization of the African Medicine Agency (AMA), emphasizing the importance of strong national regulatory authorities and increased ratification of the AMA Treaty for ensuring access to essential medical products and technologies for the African people. [Read the Full Post]

Inhibition of Diacylglycerol Acyltransferase 2 Versus Diacylglycerol Acyltransferase 1: Potential Therapeutic Implications of Pharmacology

29 | Nov 26 2023

DGAT2 inhibitors, exemplified by ervogastat, offer a promising and well-tolerated therapeutic approach for patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and NASH with liver fibrosis, in contrast to limited efficacy and adverse effects associated with DGAT1 inhibitors. [Read the Full Post]

Assessing the venous system: Correlation of mean systemic filling pressure with the venous excess ultrasound grading system in cardiac surgery

21 | Nov 20 2023

The study demonstrates a strong positive correlation between the venous excess ultrasound (VExUS) grading system and mean systemic filling pressure (Pmsf) in the early postoperative period after cardiac surgery, highlighting the critical role of systemic venous congestion in patient outcomes. [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

93 | 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]

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

63 | 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]

A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma

77 | Nov 10 2023

In this experiment, a sensitive UPLC-MS/MS method was successfully validated for quantifying oprozomib concentrations in rat plasma, demonstrating its suitability for pharmacokinetic studies and potential use in assessing the treatment of haematological malignancies, including relapsed refractory multiple myeloma. [Read the Full Post]

Experimental and Theoretical Estimations of Atrazine's Adsorption in Mangosteen-Peel-Derived Nanoporous Carbons

29 | Nov 06 2023

This study investigated the removal of atrazine using nanoporous carbons derived from mangosteen-peel chars, focusing on the role of nitrogen groups and surface chemistry, and elucidating the importance of micropores and mesopores in the adsorption process. [Read the Full Post]

Cordycepin inhibits myogenesis via activating the ERK1/2 MAPK signalling pathway in C2C12 cells

15 | Nov 05 2023

Cordycepin inhibits myoblast differentiation by downregulating MyoD and MyoG, while preserving undifferentiated reserve cell pools through upregulation of Myf5 and p130, enhancing energy reserves, and activating ERK1/2 MAPK signaling, suggesting its potential for preventing and treating degenerative muscle diseases. [Read the Full Post]

Nobiletin Mitigates D-Galactose-Induced Memory Impairment via Improving Hippocampal Neurogenesis in Mice

33 | Nov 05 2023

The study found that administration of nobiletin (NOB) attenuated memory impairment, restored hippocampal neurogenesis, reduced neuroinflammation, and improved brain function in D-galactose-induced aging mice, suggesting NOB as a potential neurogenesis enhancer for mitigating brain aging. [Read the Full Post]

Novel Glutamine Antagonist JHU395 Suppresses MYC-Driven Medulloblastoma Growth and Induces Apoptosis

18 | Nov 03 2023

The preclinical study demonstrated that the brain-targeted prodrug JHU395, derived from the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON), effectively killed MYC-expressing medulloblastoma cells, increased survival in mice with MYC-amplified medulloblastoma tumors, and showed promise for further development as a potential treatment for medulloblastoma. [Read the Full Post]

Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer

57 | Nov 01 2023

Inhibition of IRE1α in triple negative breast cancer cells leads to DGAT2-dependent accumulation of triacylglycerols (TAGs) and sensitizes the cells to nutritional stress, highlighting the importance of IRE1α RIDD activity in reprogramming cellular lipid metabolism. [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]

Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

43 | Oct 27 2023

The novel nanometer drug loading system, FZ/MER-AgMOF@Bm, effectively combats sepsis by delivering anti-inflammatory and antibacterial agents to infectious microenvironments, reducing inflammation, eliminating bacteria, and improving survival outcomes in a mouse model of sepsis. [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]

Tenuifolin in the prevention of Alzheimer's disease-like phenotypes: Investigation of the mechanisms from the perspectives of calpain system, ferroptosis, and apoptosis

35 | Oct 26 2023

Tenuifolin (Ten), an active component of Polygala tenuifolia, prevents Alzheimer's disease (AD)-like phenotypes through multiple mechanisms, including regulation of synaptic plasticity, apoptosis, calcium signaling, oxidative stress, and ferroptosis. [Read the Full Post]

Genome-wide CRISPR screening reveals key genes and pathways associated with 20-hydroxyecdysone signal transduction in the silkworm (Bombyx mori)

91 | Oct 26 2023

This study utilized a genome-wide CRISPR/Cas9-based library to identify key genes involved in the 20E signaling pathway in the silkworm, shedding light on the mechanisms underlying metamorphosis and hormone regulation. [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]

Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin

57 | Oct 06 2023

The study confirms that GPX4 acts as an oncogene, inhibits ferroptosis in cancer cells, and its inhibition enhances the anticancer effect of cisplatin. [Read the Full Post]

Preparation and Properties of Natural Polysaccharide-Based Drug Delivery Nanoparticles

83 | Oct 05 2023

The paper presents the development of RGD-(NPGP/CS)3NPGP nanoparticles through layer-by-layer assembly, which demonstrate high encapsulation efficiency, pH-sensitive release, and effective targeting to integrin receptor-expressing tumor cells, making them promising as novel anticancer drug carriers. [Read the Full Post]

Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase

50 | Oct 02 2023

This study demonstrates that increased infiltration of neutrophils and the release of neutrophil elastase play a significant role in Doxorubicin-induced cardiotoxicity, highlighting potential therapeutic interventions for this condition. [Read the Full Post]

Thalidomide derivatives as nanomolar human neutrophil elastase inhibitors: Rational design, synthesis, antiproliferative activity and mechanism of action

0 | Oct 01 2023

In this study, rationally designed human neutrophil elastase inhibitors derived from thalidomide demonstrated strong inhibitory activity, competitive mode of action, and promising antiproliferative effects against cancer cells, with compound 4f showing comparable HNE inhibition to sivelestat and inducing cell cycle arrest and apoptosis in T47D breast carcinoma cells. [Read the Full Post]

Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein

54 | Sep 28 2023

This study identified fibroblast activation protein (FAP) and dipeptidyl peptidase-4 (DPP4) as proteases responsible for cleaving the cellular prion protein (PrPC), with their activity and modulation affecting the physiology and pathogenic potential of PrPC and its associated diseases. [Read the Full Post]

Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation

25 | Sep 28 2023

The study demonstrated that pancreatic preservation with alvelestat, a neutrophil elastase inhibitor, improved the yield and function of porcine islets, suggesting its potential as a novel clinical strategy for enhancing the outcome of islet transplantation. [Read the Full Post]

Thalidomide derivatives as nanomolar human neutrophil elastase inhibitors: Rational design, synthesis, antiproliferative activity and mechanism of action

67 | Sep 27 2023

Through rational design, a series of thalidomide-derived compounds were synthesized, and compound 4f demonstrated strong inhibition of human neutrophil elastase (HNE), comparable to sivelestat, and exhibited enhanced antiproliferative activity against various cancer cell lines, inducing cell cycle arrest and apoptosis in T47D breast carcinoma cells. [Read the Full Post]

Pathway network of pyroptosis and its potential inhibitors in acute kidney injury

60 | Sep 23 2023

This article reviews the role of pyroptosis in acute kidney injury (AKI), focusing on the assembly and activation of the NLRP3 inflammasome and its downstream inflammatory cytokines as potential therapeutic targets for novel AKI therapies. [Read the Full Post]

Semi-quantification and Potency Verification of the HIV Protease Inhibitor Based on the Matrix-Capsid Protein Immobilized Nickel (II)/NTA-Tol/Graphene Oxide/SPCE Electrochemical Biosensor

37 | Sep 15 2023

The study proposes a low-cost electrochemical biosensor platform for the semi-quantification and verification of HIV protease inhibitors, offering a potential solution to expedite the discovery and development of new HIV drugs. [Read the Full Post]

Hepatocytic AP-1 and STAT3 contribute to chemotaxis in alphanaphthylisothiocyanate-induced cholestatic liver injury

76 | Sep 13 2023

The study demonstrated that the AP-1 signaling pathway is more crucial than STAT3 in mediating the inflammatory cascade of ANIT-induced CLI, and hepatocytes, rather than Kupffer cells, release chemotactic factors involved in chemotaxis during CLI. [Read the Full Post]

Integrating knowledge of protein sequence with protein function for the prediction and validation of new MALT1 substrates

130 | Sep 07 2023

The bioinformatics-led substrate discovery workflow, GO-2-Substrates, successfully identified seven new MALT1 substrates, including TANK, TAB3, CASP10, ZC3H12D, ZC3H12B, CILK1, and ILDR2, expanding the known repertoire and providing valuable insights into the function of MALT1. [Read the Full Post]

H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway induces ferroptosis in nasal mucosal epithelial cells

66 | Sep 06 2023

This study reveals that the H1N1 virus induces ferroptosis in human nasal epithelial cells via the NRF2-KEAP1-GCLC signaling pathway and glutaminolysis, contributing to nasal mucosal epithelial inflammation and suggesting a potential therapeutic target for viral-induced nasal inflammation. [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]

Downregulated XBP-1 Rescues Cerebral Ischemia/Reperfusion Injury-Induced Pyroptosis via the NLRP3/Caspase-1/GSDMD Axis

64 | Aug 08 2023

Downregulation of XBP-1 inhibits pyroptosis through the NLRP3/Caspase-1/GSDMD pathway, providing neuronal protection in the context of cerebral ischemia/reperfusion injury. [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]

Cellular senescence in the response of HR+ breast cancer to radiotherapy and CDK4/6 inhibitors

66 | Aug 06 2023

The study findings suggest that the inferiority of CDK4/6 inhibition followed by radiation therapy (P→RT) compared to radiation therapy followed by CDK4/6 inhibition (RT→P) in preclinical models of HR+ breast cancer may be partially attributed to the differential accumulation of senescent cells in the tumor microenvironment. [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]

Transformable prodrug nanoplatform via tumor microenvironment modulation and immune checkpoint blockade potentiates immunogenic cell death mediated cancer immunotherapy

65 | Aug 04 2023

In this study, a dual-responsive polymersomal prodrug nanoplatform was developed, combining CAF inhibition, ROS consumption, immune checkpoint blockade, and immunogenic cell death induction, leading to improved tumor regression and long-term immune memory response, offering potential for effective cancer treatment. [Read the Full Post]

pH-sensitive smart indicators based on cellulose and different natural pigments for tracing kimchi ripening stages

159 | Jul 27 2023

The study found that cellulose-based pH-sensitive indicators loaded with natural pigments showed more pronounced color changes in response to lactic acid and pH variations, with alkalized indicators being particularly effective for monitoring the fermentation process of acidic foods such as kimchi. [Read the Full Post]

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

45 | 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]

Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR

40 | Jul 17 2023

Shikonin, a recently identified inhibitor of the DNA damage response (DDR), has been found to suppress DDR activation by targeting ATM and ATRIP, leading to enhanced anti-cancer effects of chemotherapy, making it a potential candidate for chemotherapy sensitization. [Read the Full Post]

Hexavalent chromium disrupts the skin barrier by targeting ROS-mediated mitochondrial pathway apoptosis in keratinocytes

51 | Jul 17 2023

This study demonstrates that hexavalent chromium (Cr(VI)) exposure leads to skin deterioration, hemorrhaging, collagen fiber layer thinning, impaired membrane integrity, and apoptosis primarily targeting keratinocytes, highlighting the importance of apoptosis and ROS-mediated mitochondrial pathway in Cr(VI)-induced skin barrier injury. [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]

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]

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors

49 | Jul 12 2023

The phase 3 clinical trial showed that nirogacestat, an oral γ-secretase inhibitor, significantly improved progression-free survival, objective response rates, and patient-reported outcomes while presenting common but mostly low-grade adverse events in adults with progressing desmoid tumors. [Read the Full Post]

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

119 | Jul 12 2023

In this study, the researchers demonstrated that timing the inhibition of the Notch signaling pathway in human retinal organoids can enhance and synchronize the differentiation of photoreceptor cells, potentially leading to an enriched population of early cone or rod photoreceptors for transplantation therapies in vision loss disorders. [Read the Full Post]

PCSK9 Inhibition Regulates Infarction-Induced Cardiac Myofibroblast Transdifferentiation via Notch1 Signaling

30 | Jul 09 2023

SBC-115076, a PCSK9 inhibitor, was found to mitigate cardiac fibrosis and improve ventricular function after myocardial infarction by inhibiting the differentiation of cardiac fibroblasts to myofibroblasts through the Notch1/Hes1 signaling pathway. [Read the Full Post]

Fangchinoline Exerts Anticancer Effects on Colorectal Cancer Cells by Evoking Cell Apoptosis via Endoplasmic Reticulum Stress

92 | Jul 04 2023

Fangchinoline (FAN) induces apoptosis in human colorectal cancer cells by activating endoplasmic reticulum stress through the upregulation of ER stress-related proteins and the involvement of the CHOP pathway. [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]

Celastrol inhibits necroptosis by attenuating the RIPK1/RIPK3/MLKL pathway and confers protection against acute pancreatitis in mice

0 | Jun 27 2023

Celastrol demonstrates potential as a therapeutic agent for inhibiting necroptosis and reducing the severity of necroptotic-related diseases such as pancreatitis [Read the Full Post]

Deciphering the mechanism of PSORI-CM02 in suppressing keratinocyte proliferation through the mTOR/HK2/glycolysis axis

64 | Jun 26 2023

PSORI-CM02 exhibits anti-proliferative effects on psoriatic keratinocytes by inhibiting the mTOR/HK2/glycolysis axis, as demonstrated in both in vitro and in vivo models. [Read the Full Post]

Characterization of cell line with dedifferentiated GIST-like features established from cecal GIST of familial GIST model mice

50 | Jun 21 2023

The study established a cell line derived from cecal GIST in a familial GIST mouse model, characterized as dedifferentiated GIST-like cells with high expression of HSP90 families and glutaminase 1, and identified the combination of Pimitespib and Telaglenastat as a potential treatment strategy for these cells. [Read the Full Post]

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

87 | 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]

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

0 | Jun 17 2023

This study identified potential lead compounds, including natural-product-derived compounds and approved drugs, that have the potential to be developed as anti-Ebola drugs, pending further experimental testing. [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]

Wolbachia Ferrochelatase as a potential drug target against filarial infections

90 | Jun 16 2023

Targeting the ferrochelatase enzyme in Wolbachia's heme biosynthetic pathway presents a potential therapeutic strategy for filarial infections, leading to the discovery of four promising drug candidates that can inhibit the worms' growth and survival. [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]

Targeting mitochondrial energetics reverses panobinostat- and marizomib-induced resistance in pediatric and adult high-grade gliomas

22 | Jun 12 2023

This study investigates the molecular mechanisms and vulnerabilities associated with acquired resistance to the combination therapy of panobinostat and marizomib in high-grade gliomas, highlighting the importance of targeting glycolysis and mitochondrial function to overcome resistance. [Read the Full Post]

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

47 | Jun 11 2023

This review summarizes the available in vitro and in vivo data on the role of proteasome inhibitors (PrIn) in medullary thyroid cancer (MTC) and highlights the need for further clinical trials to explore their potential as a treatment option for MTC patients. [Read the Full Post]

OONO-/MMP2/MMP9 pathway-mediated apoptosis of porcine granulosa cells is associated with DNA damage

64 | Jun 09 2023

The passage describes a new mechanism for porcine follicular atresia involving peroxynitrite anion, which can increase the expression of matrix metalloproteinase 2 and 9, resulting in DNA damage, inhibition of DNA repair and apoptosis of granulosa cells. [Read the Full Post]

S-1-propenyl-L-cysteine suppresses lipopolysaccharide-induced expression of matrix metalloproteinase-1 through inhibition of tumor necrosis factor-α converting enzyme-epidermal growth factor receptor axis in human gingival fibroblasts

30 | Jun 09 2023

S-1-propenyl-L-cysteine, a sulfur bioactive compound found in aged garlic extract, suppresses the expression of matrix metalloproteinase-1 through inhibition of the tumor necrosis factor-α converting enzyme-epidermal growth factor receptor axis in gingival fibroblasts, suggesting it may be an effective therapeutic agent for periodontal disease. [Read the Full Post]

Apigenin Alleviated High-Fat-Diet-Induced Hepatic Pyroptosis by Mitophagy-ROS-CTSB-NLRP3 Pathway in Mice and AML12 Cells

50 | Jun 08 2023

This passage describes a study on the effects of apigenin on liver injury caused by a high-fat diet and palmitic acid-induced pyroptosis in liver cells through the mitophagy-ROS-CTSB-NLRP3 pathway. [Read the Full Post]

Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B

105 | Jun 08 2023

The study investigated the pH-dependent inhibitory properties of CA-074, a selective inhibitor of cathepsin B, and found it to be more effective at inhibiting cathepsin B at an acidic pH of 4.6 with nM potency, while maintaining its specificity for cathepsin B over other cysteine cathepsins under both acidic and neutral pH conditions. [Read the Full Post]

DEEMD: Drug Efficacy Estimation Against SARS-CoV-2 Based on Cell Morphology With Deep Multiple Instance Learning

58 | Jun 07 2023

DEEMD is a computational pipeline using deep neural network models within a multiple instance learning framework to identify putative treatments effective against SARS-CoV-2 based on morphological analysis of the RxRx19a dataset. [Read the Full Post]

Astragaloside IV Alleviates Brain Injury Induced by Hypoxia via the Calpain-1 Signaling Pathway

73 | Jun 07 2023

AS-IV can inhibit hypoxia-induced oxidative stress and apoptosis in hippocampal neurons by downregulating the calpain-1/HIF-1α/caspase-3 pathway. [Read the Full Post]

Characterization of a Novel Milk-Clotting Aspartic Protease from Penicillium sp. and Structural Explanation for its High Milk-Clotting Index

77 | Jun 06 2023

PsMCE is a novel milk-clotting enzyme with specific hydrolysis activity on κ-casein proteins and potential applications in cheese making due to its thermolability and high milk-clotting index value. [Read the Full Post]

Potential drug discovery for COVID-19 treatment targeting Cathepsin L using a deep learning-based strategy

15 | Jun 06 2023

The study suggests that CTSL could be a promising therapeutic target for COVID-19, and the researchers used Chemprop to identify small molecules and FDA-approved drugs that can block CTSL activity, finding five molecules and drugs that can inhibit the activity of CTSL and inhibit the infection of both pseudotype and live SARS-CoV-2, including daptomycin. [Read the Full Post]

Protective Effect of Calpain Inhibition During Cold Ischemia on Ischemia-reperfusion Injury After Lung Transplantation

24 | Jun 06 2023

The study showed that the administration of ALLN during cold ischemia improves IR lung injury in a lung transplant animal model by suppressing necroptosis. [Read the Full Post]

Canine distemper virus N protein induces autophagy to facilitate viral replication

62 | Jun 06 2023

This study revealed that CDV N protein induces complete autophagy to facilitate viral replication, providing new insights into the interaction between CDV and the host autophagy machinery. [Read the Full Post]

Identification of Embryonic Chicken Proteases Activating Newcastle Disease Virus and Their Roles in the Pathogenicity of Virus Used as In Ovo Vaccine

26 | Jun 05 2023

The study identified five trypsin-like proteases that activate NDV in chicken embryos and found that the F protein with a 3B-FCS was crucial for the attenuation of NDV, providing a potential target for the rational design of safe in ovo ND vaccines. [Read the Full Post]

Phytochemical characterization, antioxidant activity and antihypertensive evaluation of Ocimum basilicum L. in l-NAME induced hypertensive rats and its correlation analysis

89 | Jun 05 2023

The study found that Ocimum basilicum Linn. leaves extracts have potential as antihypertensive drugs due to their bioactive metabolites, with phenolic compounds playing a role in inhibiting l-Name induced hypertension and flavonoids contributing to antioxidant activities. [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]

Smad7 Is Highly Expressed in Human Degenerative Discs and Participates in IL-1 β-Induced Apoptosis of Rat AF Cells via the Mitochondria Pathway

40 | Jun 03 2023

Smad7 participates in IL-1β-induced apoptosis of rat annulus fibrosus cells via the mitochondria pathway and may be a potential target for the prevention and treatment of degenerative disc disease. [Read the Full Post]

Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats

31 | May 29 2023

The study suggests that concomitant administration of gallic acid and the SGK1 gene inhibitor GSK650394 may have a more beneficial effect on cardiac ischemia/reperfusion injury than each drug alone. [Read the Full Post]

Targeting tumour-associated macrophages in hodgkin lymphoma using engineered extracellular matrix-mimicking cryogels

15 | May 25 2023

The researchers used a biomimetic cryogel model to screen for invasion inhibitors and identified five drug hits, including ruxolitinib and PD-169316, which decreased tumor-associated macrophage invasion and modulated macrophage polarization in Hodgkin lymphoma. [Read the Full Post]

Combination of endothelial progenitor cells and BB-94 significantly alleviates brain damage in a mouse model of diabetic ischemic stroke

16 | May 25 2023

EPCs and the matrix metalloproteinase inhibitor BB-94 may have protective effects against ischemic stroke by reducing the expression of MMPs, as demonstrated in both in vitro and in vivo experiments. [Read the Full Post]

Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3

16 | May 25 2023

The study found that Bacillus anthracis peptidoglycan inhibits the capacity of human monocyte-derived macrophages to efferocytose apoptotic cells by reducing cell surface expression of efferocytic receptors, dependent on human serum opsonins and involving proteases. [Read the Full Post]

Metalloprotease domain latency protects ADAMTS13 against broad-spectrum inhibitors of metalloproteases while maintaining activity towards VWF

43 | May 25 2023

The study found that the metalloprotease domain of ADAMTS13 protects it from inhibitors and exists in a latent state that is partially maintained by loops flanking the S1 and S1' specificity pockets. [Read the Full Post]

Mutiple myeloma resistant to melphalan (NSC-8806) treated with cyclophosphamide (NSC-26271), prednisone (NSC-10023), and chloroquine (NSC-187208)

41 | May 17 2023

This prospective randomized study compared the effectiveness of two therapeutic regimens in 41 patients with multiple myeloma resistant to melphalan, with no significant differences in response or toxicity observed between the groups, despite the addition of chloroquine to one regimen. [Read the Full Post]

A myeloid leukemia factor homolog is involved in tolerance to stresses and stress-induced protein metabolism in Giardia lamblia

37 | May 16 2023

This study investigated the role of MLF vesicles in G. lamblia and found that they share similar stress-induced characteristics with autophagy compartments and are important for survival in stress conditions. [Read the Full Post]

Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway

31 | May 15 2023

Inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway, making MALT1 a potential therapeutic target for treating myocardial infarction. [Read the Full Post]

BC-1215 inhibits ATP-induced IL-1β secretion via the FBXL2-mediated ubiquitination and degradation of not only NLRP3, but also pro-IL-1β in LPS-primed THP-1 cells

39 | May 10 2023

BC-1215, an inhibitor of FBXO3, suppresses ATP-induced IL-1β secretion in LPS-primed THP-1 cells via the FBXL2-mediated ubiquitination and degradation of NLRP3 and pro-IL-1β, making FBXO3 a potential therapeutic target for inflammatory diseases. [Read the Full Post]

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

37 | May 05 2023

This study used an in silico approach to identify potential small molecule inhibitors of the Ebola virus by targeting the N-terminal domain of VP40, resulting in the identification of several natural-product-derived compounds and approved drugs with potential anti-EBOV activity that can be further explored for EVD treatment. [Read the Full Post]

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy

48 | May 04 2023

The study found that although HCV cure may play a positive role in renal function in CKD stage 3b-4, long-term mortality remained high among end-stage CKD patients, with no improvement in renal function observed and a high proportion of patients requiring kidney transplantation. [Read the Full Post]

Potential drug candidates as P-glycoprotein inhibitors to reverse multidrug resistance in cancer: an in silico drug discovery study

28 | May 04 2023

This study aimed to identify potential P-glycoprotein inhibitors for the treatment of carcinoma using in silico techniques, and identified five promising drug candidates with high binding energies and good pharmacokinetic properties. [Read the Full Post]

Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1

26 | May 03 2023

The discovery that dasabuvir, an FDA-approved drug for HCV treatment, acts as a ROCK1 inhibitor and suppresses ESCC growth through blocking ROCK1/ERK signaling pathway provides a promising candidate for further investigation as an anti-cancer therapy for ESCC. [Read the Full Post]

Structural and functional characterization of RNA dependent RNA polymerase of Macrobrachium rosenbergii nodavirus (MnRdRp)

34 | May 03 2023

The study provides insights into the structure and potential drug targeting of MnRdRp, the RNA-dependent RNA polymerase of the MrNV virus that causes white tail disease in farmed Macrobrachium rosenbergii. [Read the Full Post]

The effect of different direct antivirals on hepatic steatosis in nondiabetic and naïve hepatitis C-infected Egyptian patients

35 | May 03 2023

This study found that achieving sustained virological response after 12 weeks of treatment with direct antiviral drugs improved the metabolic profile and reduced hepatic steatosis and fibrosis in nondiabetic, chronically infected HCV Egyptian patients naive to any form of HCV treatment, but was also associated with an increase in LDL mostly due to viral-host molecular interaction. [Read the Full Post]

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease

38 | May 03 2023

The study showed that ombitasvir/paritaprevir/ritonavir-based therapy is highly effective and safe in chronic HCV patients with CKD, with the highest SVR achieved with ombitasvir/paritaprevir/ritonavir plus ribavirin. [Read the Full Post]

Assessment of alteration in antiviral plasma concentration across dialysis days: computational and analytical study

35 | May 03 2023

This study found that protein-bound uremic toxins have a lower binding affinity than directly acting antivirals, indicating a reduced liability of competitive displacement and suggesting that PBUT accumulation may have limited effect on the disposition of DAAs. [Read the Full Post]

A large-scale functional analysis of genes expressed differentially in insulin secreting MIN6 sublines with high versus mildly reduced glucose-responsiveness

43 | May 01 2023

This study identified 18 genes that altered glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells, and confirmed Sox11 as a negative regulator of insulin secretion and its role in glucose metabolism. [Read the Full Post]

Development of UPLC method for simultaneous assay of some COVID-19 drugs utilizing novel instrumental standard addition and factorial design

29 | Apr 30 2023

The proposed method is a green, rapid, and simple RP-UPLC method developed and optimized by full factorial design for the simultaneous separation of oseltamivir phosphate, daclatasivir dihydrochloride, and remdesivir, with dexamethasone as a co-administered drug, and it demonstrated linearity, precision, and accuracy with low limits of quantitation and detection, and high percentage recoveries, making it an eco-friendly and efficient analytical procedure. [Read the Full Post]

Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats

35 | Apr 29 2023

The study investigated the effect of six drugs on the transport of gadoxetate in rats using PBPK modelling and tracer-kinetic models, demonstrating a framework for prospective quantification of hepatic transporter-mediated DDI in humans. [Read the Full Post]

Analysis of Hepatitis C Virus Resistance-Associated Substitutions in Direct-Acting Antiviral Failure in South Korea Using Next-Generation Sequencing

27 | Apr 29 2023

This study found that retreatment with pan-genotypic DAA was highly successful in Korean patients with chronic HCV infection who failed initial DAA treatment, despite the presence of baseline or treatment-emergent RAS. [Read the Full Post]

The CNC-family transcription factor Nrf3 coordinates the melanogenesis cascade through macropinocytosis and autophagy regulation

68 | Apr 24 2023

The research shows that the transcription factor Nrf3 regulates macropinocytosis and autophagy to coordinate melanogenesis, and has potential therapeutic implications for hyperpigmentation disorders and as an anti-melanogenic target in HIV-1 infected individuals taking nelfinavir. [Read the Full Post]

Targeting chromosome 12q amplification in relapsed glioblastoma: the use of computational biological modeling to identify effective therapy-a case report

66 | Apr 24 2023

The case report demonstrates the utility of biosimulation in identifying effective treatment options based on comprehensive genomic abnormalities and highlights a promising treatment combination for GBM and potentially other cancers harboring chromosome 12q amplification. [Read the Full Post]

Safety and efficacy of WC2031 versus vibramycin for the treatment of uncomplicated urogenital Chlamydia trachomatis infection: a randomized, double-blind, double-dummy, active-controlled, multicenter trial

40 | Apr 23 2023

The study found that a once-daily, delayed-release formulation of doxycycline hyclate (WC2031) was noninferior to twice-daily Vibramycin for the treatment of uncomplicated urogenital chlamydia and was better tolerated, with comparable safety. [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]

SARS-CoV-2 Main Protease Drug Design, Assay Development, and Drug Resistance Studies

106 | Apr 21 2023

This Account describes efforts to develop covalent and noncovalent inhibitors of the SARS-CoV-2 main protease and the identification of nirmatrelvir-resistant mutants, providing guidance for the development of effective antivirals against COVID-19. [Read the Full Post]

Adequacy of energy and macronutrients intake in differently active slovenian adolescents

131 | 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]

Sitagliptin inhibits the survival, stemness and autophagy of glioma cells, and enhances temozolomide cytotoxicity

21 | Apr 21 2023

Sitagliptin shows promise as a potential antiglioma drug to overcome TMZ resistance and enhance the therapeutic efficacy of GBM treatment. [Read the Full Post]

An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii

36 | Apr 20 2023

An unconventional SNARE complex comprising TgStx1, TgStx20, and TgStx21 mediates vesicular fusion at the plasma membrane in T. gondii, indicating a unique mechanism for exocytosis in this organism. [Read the Full Post]

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options

37 | Apr 20 2023

The study suggests that a stratified treatment cascade with SOF/VEL for cirrhotic patients and SOF/DAC for non-cirrhotic patients in Malaysia is a cost-saving approach. [Read the Full Post]

Safety and efficacy of elbasvir/grazoprevir in patients infected with hepatitis C virus genotype 4 in Qassim region of Saudi Arabia

16 | Apr 20 2023

The study found that the elbasvir/grazoprevir (EBR-GZR) treatment regimen for 12 weeks is safe and effective in achieving sustained virological response (SVR12) in HCV genotype 4-infected treatment-naïve Saudi patients, with improvement in prognostic markers of liver disease in participants with compensated cirrhosis. [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]

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

110 | Apr 11 2023

The study investigates the role of nerve growth factor and its receptor, tropomyosin receptor kinase A, in triple-negative breast cancer and suggests that targeting TrkA may be a potential therapeutic strategy for this disease. [Read the Full Post]

Neutralization of NET-associated human ARG1 enhances cancer immunotherapy

40 | Apr 09 2023

The study investigates the role of neutrophil extracellular traps (NETs) and cathepsin S (CTSS) in regulating the activity of arginase 1 (ARG1) in pancreatic ductal adenocarcinoma (PDAC) and suggests the potential of targeting extracellular ARG1 with monoclonal antibodies as a therapeutic approach for PDAC in combination with immune checkpoint inhibitors. [Read the Full Post]

The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma

51 | Apr 09 2023

Combining carfilzomib with nelfinavir shows superior efficacy in inducing proteotoxicity and endoplasmic reticulum stress in non-small-cell-lung carcinoma (NSCLC) compared to the combination of bortezomib and nelfinavir, and may represent a future treatment option for NSCLC. [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]

Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture

99 | Mar 30 2023

The study suggests that targeting the Hedgehog signaling pathway and cancer stem cells using inhibitors like AY9944 and GANT61 can improve the sensitivity of anti-cancer drug treatment in colorectal tumor patient-derived ALI organoids and may be a useful combinational therapeutic strategy against metastatic colorectal cancer. [Read the Full Post]

Towards personalized treatment with clozapine

114 | Mar 30 2023

This study found that clozapine was more effective when used as a first- or second-line treatment, and identified factors associated with response to clozapine treatment and side effects, which could aid in the development of personalized treatment approaches for individuals with treatment-resistant schizophrenia. [Read the Full Post]

The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis

54 | Mar 28 2023

Aberrant lipid metabolism, specifically increased triglyceride levels, stimulates CD4+ T cells and promotes Th1 and Th17 cell differentiation in the pathogenesis of autoimmune uveitis, and inhibition of TAG generation using A922500 can ameliorate the disease severity by down-regulating Th17 cell response and promoting apoptosis-related protein expression. [Read the Full Post]

Age-related cataract: GSTP1 ubiquitination and degradation by Parkin inhibits its anti-apoptosis in lens epithelial cells

55 | Mar 26 2023

This study demonstrates that oxidative stress-induced apoptosis of lens epithelial cells in age-related cataract is regulated by E3 ligase Parkin-mediated degradation of GSTP1, providing potential targets for ARC therapy. [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]

Sterol O-Acyltransferase Inhibition Ameliorates High-Fat Diet-Induced Renal Fibrosis and Tertiary Lymphoid Tissue Maturation after Ischemic Reperfusion Injury

67 | Mar 17 2023

High-fat diet-induced renal tertiary lymphoid tissues and sustained inflammation in mice with ischemic reperfusion injury were found to be associated with sterol O-acyltransferase (SOAT) 1-dependent cholesteryl ester accumulation, and SOAT1 inhibition was found to attenuate TLT formation and renal inflammation, suggesting its potential as a therapeutic target for CKD prevention and treatment. [Read the Full Post]

Blocking Cholesterol Metabolism with Tumor-Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy

110 | Mar 17 2023

Researchers have designed matrix metalloproteinase-2-sensitive tumor-penetrable nanovesicles that can regulate cholesterol metabolism to enhance photodynamic cancer immunotherapy by reinvigorating the functions of CD8+ T cells and suppressing the migration of tumor cells. [Read the Full Post]

Intravenous dabigatran provides adequate anticoagulation for cardiopulmonary bypass using a rabbit model

67 | Mar 17 2023

The study demonstrated that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis in a rabbit CPB model, providing a potential alternative anticoagulant approach to heparin. [Read the Full Post]

Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of dabigatran etexilate, intermediate metabolite and dabigatran in 50μL rat plasma and its application to pharmacokinetic study

25 | Mar 17 2023

A simple, rapid, and specific LC-MS/MS method has been developed for the simultaneous determination of dabigatran etexilate and its metabolites in rat plasma, which has been successfully applied to a pharmacokinetic study following a single oral administration of 15mg/kg dabigatran etexilate. [Read the Full Post]

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation

117 | Mar 16 2023

The study suggests that proteasome inhibitors may cause cardiotoxicity through stress response and mitochondrial dysfunction, which highlights the need for further studies to develop strategies to minimize their side effects. [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]

Concentration dependence of active potassium transport in the human red blood cell in the presence of inhibitors

110 | Mar 09 2023

The passage describes the inhibition of active potassium influx in human red blood cells by several compounds, including strophanthidin, ethacrynic acid, and MK-870, and suggests a model for the behavior of the transport system in the presence of these compounds and potassium ions. [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]

Metabolic characterization and GAPDH dependent regulation of ENaC in hPheo1 wild-type and SDHB knockdown cells

51 | Mar 08 2023

The study investigates the expression and activity of ENaC and ASIC ion channels in hPheo1 WT and SDHB KD cells, which may provide important insights into understanding and treating SDHB-related disease. [Read the Full Post]

In-vitro dynamic dissolution/bioconversion/permeation of fosamprenavir using a novel tool with an artificial biomimetic permeation barrier and microdialysis-sampling

38 | Mar 02 2023

A novel cell-free in vitro setup was developed and tested to evaluate the dynamic dissolution, bio-conversion, and permeation of fosamprenavir, showing promising results for gaining a deeper understanding of the bioconversion and permeation of phosphate-ester prodrugs. [Read the Full Post]

Understanding the impact of halogen functional group (Br, Cl, F, OH) in amprenavir ligand of the HIV protease

93 | Mar 01 2023

Study provides valuable insights into the structure-activity relationship of protein-ligand interactions in HIV/AIDS research and highlights the importance of halogen and hydrogen bond interactions in the development of new antiviral drugs. [Read the Full Post]

Understanding drug resistance patterns across different classes of antiretrovirals used in HIV-1-infected treatment-Naïve and experienced patients in Mumbai, India

43 | Feb 28 2023

The study found that treatment-experienced patients had higher incidence of high-level resistance to antiretroviral drugs compared to treatment-naive patients, with a positive correlation observed for within class resistance across antiretrovirals, and highlights the importance of genotypic drug resistance testing before starting treatment. [Read the Full Post]

LY450139 Inhibited Ti-Particle-Induced Bone Dissolution via Suppressing Notch and NF-κB Signaling Pathways

55 | Feb 27 2023

The study found that LY450139 has the potential to prevent the failure of joint implants by inhibiting the formation of osteoclasts, which break down bone, through the inhibition of the NF-κB and Notch signaling pathways. [Read the Full Post]

Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

48 | Feb 24 2023

Aminopeptidases play a crucial role in cellular processes and functions, including metabolism, signaling, angiogenesis, and immunology, and their overexpression in tumor cells can facilitate rapid proliferation, leading to potential use as a targeted approach for new oncological treatments. [Read the Full Post]

A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial

54 | Feb 24 2023

The "Pick-a-Winner" LI-1 trial of 243 older acute myeloid leukemia (AML) patients who were not suitable for intensive treatment showed no statistically significant improvement in complete remission, overall response, or overall survival with the addition of tosedostat, a selective oral aminopeptidase inhibitor, to low-dose cytosine arabinoside. [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]

Bowen's disease on two different unrelated anatomical sites (genitals and nail) in succession in an immunocompromised patient

53 | Feb 21 2023

A 43-year-old immunocompromised male with a history of multiple unprotected sexual exposures was diagnosed with verruca vulgaris and pigmented Bowen's disease on biopsy of hyperpigmented lesions on his genitals, and later developed longitudinal melanonychia with a subungual hyperpigmented mass on his right middle finger nail which was treated successfully with 5-fluorouracil and podophyllin. [Read the Full Post]

HIV-Tat Exacerbates the Actions of Atazanavir, Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2)

74 | Feb 21 2023

The study shows that HIV-Tat, ATV, EFV, and RTV can bind to and modulate the activity of the type 2 ryanodine receptor (RyR2) in the heart and that HIV-Tat can exacerbate the actions of ATV, EFV, and RTV on RyR2, potentially increasing the risk of cardiac arrhythmias and sudden cardiac death. [Read the Full Post]

Predicting the systemic exposure and lung concentration of nafamostat using physiologically-based pharmacokinetic modeling

51 | Feb 18 2023

This study used a physiologically based pharmacokinetic (PBPK) approach and global sensitivity analysis to predict and evaluate the pharmacokinetic profiles of nafamostat in a virtual healthy population under various dosing regimens and found that the approach is valuable in predicting the PK profile and designing an appropriate dosage regimen for the treatment of COVID-19. [Read the Full Post]

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer

105 | Feb 17 2023

Stored samples at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection in horses, but heparin interference should be considered when using homemade heparin syringes and other metabolites are stable for only 8 hours. [Read the Full Post]

Change in Cutibacterium acnes phylotype abundance and improvement of clinical parameters using a new dermocosmetic product containing Myrtus communis and Celastrol enriched plant cell culture extracts in patients with acne vulgaris

116 | Feb 15 2023

The new dermocosmetic product containing Myrtus communis and Celastrol-enriched plant cell culture extracts improved acne severity by decreasing pro-pathogen phylotype IC and increasing non-pathogen phylotype IB of Cutibacterium acnes and decreasing acne lesion count and improving the Global Evaluation Acne score. [Read the Full Post]

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1

51 | Feb 14 2023

A text-mining-based web-server tool was used to identify peroxiredoxin 1 (PRDX1) as the ROS-manipulating target of Celastrol, a natural product isolated from the plant Thunder God Vine, and the anti-tumor efficacy of Celastrol was reduced in colorectal cancer cells by inhibiting PRDX1, and a new derivative compound 19-048 with improved potency against PRDX1 was synthesized. [Read the Full Post]

Effectiveness of different treatment regimens on patients with COVID-19, hospitalized in Sanandaj hospitals: a retrospective cohort study

37 | Feb 03 2023

The study found that the drug regimen 2 (Interferons (ReciGen/Ziphron) or Interferon Vectra (lopinavir/ritonavir)) increased the days of hospitalization and hospitalization in ICU, while other drug regimens had no significant effect on mortality, use of a ventilator, or reducing mortality compared to the others. [Read the Full Post]

Awareness on current status of usage of ritonavir in the management of covid among dental students

47 | Feb 03 2023

A survey of 100 dental students in Chennai showed that postgraduate students had greater knowledge of the current use of Ritonavir in the management of COVID-19, but the study highlights the need for regular education and training programs for all healthcare workers on COVID-19 infection control procedures. [Read the Full Post]

The impact of medication on osseointegration and implant anchorage in bone determined using removal torque-A review

80 | Jan 20 2023

Martina Jolic et al. confirmed that factors such as bone quality underpined biomechanical anchorage of metal implants. [Read the Full Post]

A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy

21 | Jan 19 2023

Dengke Li et al. discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. [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]

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]

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]

Optimizing the value of lenalidomide maintenance by genetic profiling - an analysis of 556 Myeloma XI trial patients

80 | Dec 30 2022

Aikaterini Panopoulou et al. found that extended genetic profiling identified patients deriving exceptional benefit from Len maintenance. [Read the Full Post]

Desensitization Protocol to Lenalidomide: An Effective and Safe Treatment Modality for Delayed Hypersensitivity-induced Rash in Patients with Multiple Myeloma

138 | Dec 29 2022

Oded Shamriz et al. thought that desensitization to lenalidomide was safe and effective. [Read the Full Post]

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial

113 | Dec 23 2022

Kwee Yong et al. thought that KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggested that further studies were warranted to explore deferred autologous HSCT in some subgroups. [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]

Epoxomicin, a Selective Proteasome Inhibitor, Activates AIM2 Inflammasome in Human Retinal Pigment Epithelium Cells

28 | Dec 07 2022

Iswariyaraja Sridevi Gurubaran et al. thought that a selective proteasome inhibitor was a potent inflammasome activator in human RPE cells. [Read the Full Post]

Notch signaling-induced cyclin d1 in diabetes ameliorating effects of the isolated polysaccharide from Rosa canina: In vitro and in vivo studies

76 | Nov 30 2022

Soraya Sajadimajd et al. thought that upregulation of Notch signaling-induced cyclin d1 could be proposed as the underlying diabetes-reducing effects of the isolated polysaccharide derivative. [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]

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]

Target and drug predictions for SARS-CoV-2 infection in hepatocellular carcinoma patients

31 | Oct 23 2022

Luhong Wang et al. thought that COVID-19 and HCC were closely linked at the molecular level and proposes drugs that might play an important role in HCC patients with COVID-19. [Read the Full Post]

A Dentin Biomimetic Remineralization Material with an Ability to Stabilize Collagen

41 | Oct 23 2022

Siying Tao et al. indicated that PNG had great potential to combat early dentin caries for future clinical application. [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]

The CRTC-CREB axis functions as a transcriptional sensor to protect against proteotoxic stress in Drosophila

43 | Oct 02 2022

Youjie Yin et al. identified CRTC/CREB downstream ROS/JNK signaling as a conserved sensor to tackle oxidative and proteotoxic stresses. [Read the Full Post]

Arylamine N-acetyltransferase 1 deficiency inhibits drug-induced cell death in breast cancer cells: switch from cytochrome C-dependent apoptosis to necroptosis

21 | Sep 18 2022

Courtney E McAleese et al. found NAT1 deficiency could switch cell death from apoptosis to necroptosis resulting in decreased response to cytotoxic drugs. [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]

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]

Down-regulated NEDD4L facilitates tumor progression through activating Notch signaling in lung adenocarcinoma

47 | Aug 25 2022

Liping Lin et al. demonstrated that down-regulated NEDD4L facilitated LUAD progression by activating Notch signaling, and NEDD4L might be a promising target to treat LUAD. [Read the Full Post]

A Novel Defined Pyroptosis-Related Gene Signature for Predicting Prognosis and Treatment of Glioma

37 | Aug 03 2022

Zhihao Yang et al. thought that pyroptosis-related genes were of great significance for performing prognostic stratification and developing treatment strategies for glioma. [Read the Full Post]

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy

33 | Aug 03 2022

Alba García-Fernández et al. found the potential of MSNs as a versatile platform by allowing multiple combinations for gene editing and drug therapy to prepare advanced nanodevices to meet possible biomedical needs. [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]

Clostridioides difficile toxin B alone and with pro-inflammatory cytokines induces apoptosis in enteric glial cells by activating three different signalling pathways mediated by caspases, calpains and cathepsin B

61 | Jul 24 2022

Katia Fettucciari et al. demonstrated that TcdB induced caspase-dependent, mitochondria-independent enteric glial cell (EGC) apoptosis that was enhanced by the pro-inflammatory cytokines TNF-α and IFN-γ (CKs) by increasing caspase-3/7/9 and PARP activation. [Read the Full Post]

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: a retro-prospective observational study

124 | Jul 04 2022

Maria Livia Del Giudice et al. thought that Kd56 was an effective and well tolerated regimen in highly pretreated and elderly patients with a good safety profile. [Read the Full Post]

The impact of emricasan on chronic liver diseases: current data

93 | Jul 03 2022

Vasileios Lekakis et al. showed that as emricasan treatment appeared safe and well-tolerated, irrespective the severity of liver disease, more studies were required to clarify better these subgroups of patients who might benefit most from this drug. [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]

Construction and evaluation of detachable bone-targeting MOF carriers for the delivery of proteasome inhibitors

259 | Jun 17 2022

Hongbing Yang et al. provided a potential cascade targeting strategy for improving the delivery effects of bone targeted nanoparticles for the delivery of proteasome inhibitors. [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]

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells

173 | Jun 12 2022

Zhongbo Du et al. thought that the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 were promising therapeutic agents for the treatment of CRPC. [Read the Full Post]

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes

200 | Jun 11 2022

Clara Bonanad et al. it is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management. [Read the Full Post]

Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis

157 | Jun 09 2022

Md Parvez Mosharaf et al. validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. [Read the Full Post]

Inhibitory Response to CK II Inhibitor Silmitasertib and CDKs Inhibitor Dinaciclib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines

122 | Jun 09 2022

Yixuan Ma et al. thought that specific aberrations in TP53 and KRAS affected the efficacy of both inhibitors. [Read the Full Post]

CD133-Functionalized Gold Nanoparticles as a Carrier Platform for Telaglenastat (CB-839) against Tumor Stem Cells

114 | May 29 2022

Elham Poonaki et al. showed that Au-PEG-CD133-CB-839 significantly decreased the viability of CD133-postive cancer cells in a dose-dependent manner, which was higher as compared to the effects of treatment of the cells with the individual components of the assembled nanodrug. [Read the Full Post]

Rutaecarpine Attenuates Oxidative Stress-Induced Traumatic Brain Injury and Reduces Secondary Injury via the PGK1/KEAP1/NRF2 Signaling Pathway

132 | May 24 2022

Min Xu et al. showed that rutaecarpine might be a promising therapeutic agent for the treatment of TBI-related neuro-oxidative damage. [Read the Full Post]

Blue Light Induces RPE Cell Necroptosis, Which Can Be Inhibited by Minocycline

121 | May 22 2022

Weilin Song et al. provided new ideas for the pathogenesis and treatment of retinal degeneration. [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]

Biomarker guided treatment in oncogene-driven advanced non-small cell lung cancer in older adults: A Young International Society of Geriatric Oncology Report

111 | May 11 2022

Konstantinos Christofyllakis et al. thought that molecularly-guided therapy for most alterations was safe and efficacious in older adults with oncogene-driven advanced NSCLC. [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]

[Ocular toxicity of targeted therapies with MEK inhibitors and BRAF inhibitors in the treatment of metastatic cutaneous melanoma]

297 | May 06 2022

E Fauviaux et al. found that a multidisciplinary approach including ophthalmologists, dermatologists and oncologists was essential in order to adapt treatment in the advent of the ocular complications. [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]

SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer

359 | Apr 27 2022

Kiran Kundu et al. provided a rationale for lurbinectedin in combination with ATR inhibitors to overcome resistance in SCLC with low SLFN11 expression. [Read the Full Post]

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy

301 | Apr 02 2022

Jessica Cusato et al. presented data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. [Read the Full Post]

Drug repurposing through virtual screening and in vitro validation identifies tigecycline as a novel putative HCV polymerase inhibitor

270 | Apr 01 2022

Mahmoud ElHefnawi et al. found that tigecycline displayed synergistic activity with sofosbuvir and daclatasvir against HCV. [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]

Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen-glucose Deprivation

249 | Mar 24 2022

Elise Van Breedam et al. found that treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. [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]

The Natural Ligand for Metalloproteinase-A Multifaceted Drug Target

125 | Mar 15 2022

Saranya Shivashankar et al. strengthened the significance of these phytochemicals as promising lead candidates for the treatment of snakebite envenomation. [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]

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]

Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

379 | Feb 09 2022

Silu Wang et al. found the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cance. [Read the Full Post]

γ-Secretase inhibitors for breast cancer and hepatocellular carcinoma: From mechanism to treatment

383 | Feb 09 2022

Hui Jia et al. thought that the γ-secretase complex was very important for activation of the Notch receptor and regulation of target-gene transcription. [Read the Full Post]

Potential effects and application prospect of angiotensin receptor-neprilysin inhibitor in diabetic kidney disease

313 | Feb 05 2022

Xingjian Zhang found that ARNI has application potential in DKD, but there still need clinical studies that focus on DKD patients to determine its effectiveness, safety and underlying mechanism. [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]

Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation

276 | Jan 13 2022

Héctor Zapata-Carmona et al. suggested that PRKAR1 was the target of PRKA regulation by the proteasome. [Read the Full Post]

DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment

452 | Jan 06 2022

Mamta Kumari et al. found that DLL4 mAb and GSIs were expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis. [Read the Full Post]

Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

296 | Dec 23 2021

Wen Li et al. described the discovery and history of research in this pyroptosis pathway and reviewed the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. [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]

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]

SNAI1-mediated transcriptional regulation of epithelial-to-mesenchymal transition genes in breast cancer stem cells

192 | Nov 29 2021

Digvijay Singh et al. identified MMPs, a downstream effector in the SNAI1-mediated EMT regulation. [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]

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors

383 | Nov 16 2021

Analia Azaro et al. demonstrated that crenigacestat combined with different anticancer agents was poorly tolerated, leading to lowered dosing and disappointing clinical activity in patients with advanced or metastatic solid tumors. [Read the Full Post]

Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant

465 | Nov 11 2021

Rumiana Bakalova et al. thought that M/A-mediated anticancer effects were triggered by redox cycling of both substances, specifically within dysfunctional mitochondria. [Read the Full Post]

Zebrafish BID Exerts an Antibacterial Role by Negatively Regulating p53, but in a Caspase-8-Independent Manner

356 | Oct 27 2021

Zhitao Qi et al. found a novel antibacterial activity of fish Bid, providing evidence for understanding the function of apoptosis associated gene in pathogen infection. [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]

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]

γ-secretase inhibitors, DAPT and RO4929097, promote the migration of Human Glioma Cells via Smad5-downregulated E-cadherin Expression

1396 | Oct 01 2021

Shun-Fu Chang et al. showed that γ-secretase activity inhibition by DAPT and RO4929097 could promote LN18 and LN229 glioma cell migration via downregulating E-cadherin mRNA and protein expressions, but not via affecting E-cadherin protein processing. [Read the Full Post]

Protective effects of the NLRP3 inflammasome against infectious bursal disease virus replication in DF-1 cells

422 | Sep 09 2021

Zhiyuan He et al. found that IBDV could induce NLRP3 inflammasome activation in DF-1 cells through a mechanism requiring viral replication. [Read the Full Post]

VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation

393 | Sep 09 2021

Si Wen et al. found that caspase-1-mediated pyroptosis drove renal inflammation and fibrosis in diabetes. [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]

Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

566 | Aug 30 2021

Adela Kratochvilova et al. found the caspase-independent impact of FasL stimulation. [Read the Full Post]

Notch inhibitors induce diarrhea, hypercrinia and secretory cell metaplasia in the human colon

752 | Aug 30 2021

Michael Collins et al. confirmed the role of Notch signaling in intestinal homeostasis in humans. [Read the Full Post]

Sinus rhythm heart rate increase after atrial fibrillation ablation is associated with lower risk of arrhythmia recurrence

790 | Aug 11 2021

Ammar M Killu et al. showed that relative changes in HR post AF ablation correlates with AF recurrence. [Read the Full Post]

Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis

620 | Aug 10 2021

Li-Ya Mu et al. found that treatment with emricasan was more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. [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]

Outcome of COVID-19 infection in 50 multiple myeloma patients treated with novel drugs: single-center experience

1172 | Jul 27 2021

Marta Krejci et al. found that the course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths. [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]

Incidence, predictors, and outcomes of DAPT non-compliance in planned vs. ad hoc PCI in chronic coronary syndrome

903 | Jul 21 2021

Jahanzeb Malik et al. provided an insight on additional predictors of non-compliance to DAPT, helping us to identify and address specific patient-related factors for disruption. [Read the Full Post]

The mechanisms involved in the resistance of estrogen receptor-positive breast cancer cells to palbociclib are multiple and change over time

434 | Jul 19 2021

Mayu Ono et al. found that ER-positive breast cancer cells used multiple molecular mechanisms to survive in the presence of palbociclib. [Read the Full Post]

Targeting Pyruvate Kinase M2 phosphorylation reverses aggressive cancer phenotypes

555 | Jul 19 2021

Maria Apostolidi et al. found that combinations of Dinaciclib with TEPP-46 reduced cell invasion, impaired redox balance, and triggered cancer cell death. [Read the Full Post]

Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma

357 | Jul 09 2021

Sunada Khadka et al. suggested that at least for ENO1-deleted gliomas, tumors in vivo-unlike cells in culture-show limited dependence on glutaminolysis and instead primarily depended on glycolysis for anaplerosis. [Read the Full Post]

Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration

534 | Jul 05 2021

Maria Hytti et al. suggested that cellular clearance mechanisms might already be dysfunctional, and the inflammasome activated, in cells with a disease origin. [Read the Full Post]

The effects of Benjakul extract and its isolated compounds on cell cycle arrest and apoptosis in human non-small cell lung cancer cell line NCI-H226

332 | Jul 02 2021

Arunporn Itharat et al. demonstrated the effects of Benjakul and its compounds on S-G2/M or G2/M phase arrest and caspase-dependent apoptosis in lung cancer cells. [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]

Real-world-evidence-for-carfilzomib-dosing-intensity-on-overall-survival-and-treatment-progression-in-multiple-myeloma-patients

774 | Jun 13 2021

Noopur Raje found that patient outcomes could be improved if eligible MM patients are treated with the optimized [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]

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

869 | Jun 02 2021

Mark R Middleton et al. found that Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. [Read the Full Post]

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

589 | Apr 22 2021

Carolina Q Sacramento et al. found that daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, might be further fostered as an anti-COVID-19 therapy. [Read the Full Post]

Naturally Occurring Resistance Associated Substitutions in Non-Cirrhotic, Treatment Naive HCV-HIV Co-Infected Patients Does Not Affect the Treatment Response for Anti-HCV Antiviral Therapy

588 | Apr 22 2021

Ekta Gupta et al. showed that BL-RAS were common in HCV-HIV co-infected patients. [Read the Full Post]

HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

491 | 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]

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]

Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function

361 | Apr 12 2021

Congcong Wang et al. found that PRDX6 played an important antiviral role during porcine picornavirus infection, and the viral 3Cpro induced the degradation of PRDX6 to overcome PRDX6-mediated antiviral function. [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]

A proprotein convertase subtilisin/kexin type 9 inhibitor provides comparable efficacy with lower detriment than statins on mitochondria of oxidative muscle of obese estrogen-deprived rats

378 | Apr 06 2021

Chanisa Thonusin et al. showed that 17β-Estradiol exhibited the greatest efficacy on the attenuation of obesity with the least harmful effect on skeletal muscle in a model of menopause with obesity, yet its effect on the treatment of hyperlipidemia was inferior to those of standard lipid-lowering agents. [Read the Full Post]

Topical Exposure to Nemopilema nomurai Venom Triggers Oedematogenic Effects: Enzymatic Contribution and Identification of Venom Metalloproteinase

346 | Mar 29 2021

Yang Yue et al. suggested a considerable contribution of NnNV metalloproteinase-like components to the increased vasopermeability. [Read the Full Post]

Specific Inhibitor of Matrix Metalloproteinase Decreases Tumor Invasiveness After Radiofrequency Ablation in Liver Tumor Animal Model

278 | Mar 29 2021

An-Na Jiang et al. suggested that targeting the MMP process with the specific inhibition could help to increase overall ablation efficacy. [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]

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]

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment

696 | Feb 21 2021

Pilar López-Nieva et al. suggested that selective targeting γ-secretase might offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. [Read the Full Post]

Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib

672 | Feb 19 2021

Letizia Porcelli et al. unveiled a coordinate action of MAPK and Notch signaling in promoting proliferation of BRAFV600E MM and GNAQQ209L UM cells. [Read the Full Post]

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

549 | Feb 12 2021

Swathi Pathadka et al. found that in real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. [Read the Full Post]

Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis

605 | 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]

Hypoxic modulation of fetal vascular MLCK abundance, localization, and function

502 | Jan 23 2021

Dane W Sorensen et al. found that changes in MLCK distribution are a significant component of fetal vascular responses to hypoxia. [Read the Full Post]

Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation

795 | Jan 15 2021

Xinyuan Tong et al. uncovered a previously unappreciated plasticity of LKB1-deficient tumors and identified the Nanog-Notch axis in regulating gastric differentiation, which hold important therapeutic implication for the treatment of mucinous lung cancer. [Read the Full Post]

Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening

380 | Jan 02 2021

Wei Zhu et al. demonstrated a set of SARS-CoV-2 3CLpro inhibitors that might have potential for further clinical evaluation as part of drug combination therapies to treating COVID-19 patients and as starting points for chemistry optimization for new drug development. [Read the Full Post]

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

536 | 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]

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

427 | 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]

Protease inhibitors elicit anti-inflammatory effects in CF mice with Pseudomonas aeruginosa acute lung infection

262 | Dec 11 2020

A Sandri et al. thought that marimastat and Ilomastat represented candidate molecules for the treatment of CF patients, encouraging further studies on protease inhibitors and their application in inflammatory diseases. [Read the Full Post]

Betaglycan (TβRIII) is a Key Factor in TGF-β2 Signaling in Prepubertal Rat Sertoli Cells

273 | Dec 11 2020

Pradeep K Kudipudi et al. found that BG shedding served a major role in TGF-β2 signaling in Sertoli cells. [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]

Phase 1 study to evaluate Crenigacestat (LY3039478) in combination with dexamethasone in patients with T-cell acute lymphoblastic leukemia and lymphoma

602 | Nov 28 2020

Gautam Borthakur et al. found that crenigacestat demonstrated limited clinical activity at the recommended dose in adult patients with relapsed/refractory T-ALL/T-LBL. [Read the Full Post]

Brain exposure of the ATM inhibitor AZD1390 in humans - a positron emission tomography (PET) study

523 | Nov 21 2020

Aurelija Jucaite et al. found the potential of PET microdosing in predicting and guiding dose range and schedule for subsequent clinical studies. [Read the Full Post]

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

0 | Nov 20 2020

Giuseppa Augello et al. thought that association of A1210477 and MLN2238 determined synergistic antitumor effects in HCC cells. [Read the Full Post]

A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors

736 | Nov 15 2020

Haeseong Park et al. found the he combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). [Read the Full Post]

Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage

330 | Nov 04 2020

Da-Qiang Ke et al. suggested that caspase-8 inhibition alleviated subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. [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]

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]

Targeting the Notch and TGF-β signaling pathways to prevent retinal fibrosis in vitro and in vivo

827 | Sep 27 2020

Jiawen Fan et al. foung that inhibiting Notch signaling might be an effective way to prevent retinal fibrosis. [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]

Cannabinoid 1 Receptor Antagonists Play a Neuroprotective Role in Chronic Alcoholic Hippocampal Injury Related to Pyroptosis Pathway

342 | Aug 26 2020

Dingang Zhang et al. indicated that cannabinoid receptors were regulated during this process, which suggested promising therapeutic strategies against alcohol-induced neurotoxicity through pharmacologic inhibition of CB1R. [Read the Full Post]

Pyroptosis is involved in the inhibitory effect of FL118 on growth and metastasis in colorectal cancer

339 | Aug 26 2020

Zhenxue Tang et al. found that FL118 restrained the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provided important evidence in the study on the role of pyroptosis and different tumors. [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]

Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer

765 | Aug 12 2020

Moran Yang et al. found that JAG2+TANs were closely linked to IL-8-driven immune evasion microenvironment and might serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity. [Read the Full Post]

Giardia duodenalis induces extrinsic pathway of apoptosis in intestinal epithelial cells through activation of TNFR1 and K63 de-ubiquitination of RIP1 in vitro

502 | Aug 11 2020

Lin Liu et al. suggested that Giardia trophozoite stimulation could activate CASP3/8 signaling pathways via activation of TNFR1 and K63 de-ubiquitination of RIP1 caused by up-regulated expressions of CYLD and A20, and promoted Caco-2 cell apoptosis. [Read the Full Post]

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

942 | Aug 07 2020

Sihua Liu et al. indicated that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections. [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]

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

776 | Jul 16 2020

Beata Holkova et al. showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. [Read the Full Post]

Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19)

559 | Jul 15 2020

Jason Kim et al. highlighted the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warranted further investigation for established and emerging disease processes. [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

811 | 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]

Sequential Bortezomib and Temozolomide Treatment Promotes Immunological Responses in Glioblastoma Patients With Positive Clinical Outcomes: A Phase 1B Study

939 | Jun 25 2020

Mohummad A Rahman et al. found that Sequential BTZ + TMZ treatment was safe and promotes Th1-driven immunological responsed in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)). [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]

Notch Signaling Pathway Is a Potential Therapeutic Target for Extracranial Vascular Malformations

0 | Jun 22 2020

Reema B Davis et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

A Systematic Review of the Studies That Evaluate the Performance of the DAPT Score

823 | Jun 21 2020

Chun Shing Kwok et al. showd that the DAPT score had modest predictive value for ischemic and bleeding outcomes.A prospective randomized controlled trial was needed to evaluate the clinical benefits of utilising the DAPT score in guiding continued DAPT therapy beyond 1 year. [Read the Full Post]

Targeting the Ubiquitin-Proteasome Pathway to Overcome Anti-Cancer Drug Resistance

467 | Jun 20 2020

Silpa Narayanan et al. discussed various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents. [Read the Full Post]

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

858 | Jun 18 2020

Ply Chichareon et al. found that the DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. [Read the Full Post]

Prediction of Therapeutic Outcome and Survival in a Transgenic Mouse Model of Pancreatic Ductal Adenocarcinoma Treated With Dendritic Cell Vaccination or CDK Inhibitor Using MRI Texture: A Feasibility Study

428 | Jun 17 2020

Aydin Eresen et al. demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes. [Read the Full Post]

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

492 | Jun 16 2020

Erik B Faber et al. detailed the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increased the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. [Read the Full Post]

Pyruvate Anaplerosis Is a Mechanism of Resistance to Pharmacological Glutaminase Inhibition in Triple-Receptor Negative Breast Cancer

402 | Jun 02 2020

Dean C Singleton et al. highlighted the potential influence that both circulating and tumour-derived pyruvate could have on glutaminase inhibitor efficacy. Furthermore, they highlighted the benefits of 3D spheroid cultures to model the features of the tumour microenvironment and improved the in vitro investigation of cancer metabolism-targeted therapeutics. [Read the Full Post]

MG-132 Attenuates Cardiac Deterioration of Viral Myocarditis via AMPK Pathway

446 | May 28 2020

Xin-Min Zhang et al. found that MG-132 modulated apoptosis and inflammation, improved hemodynamics, and inhibited the structural remodeling of ventricles in a myocarditis mouse model via regulation of the AMPK signal pathway. [Read the Full Post]

Inhibition of Apoptosis by Caspase Inhibitor Z-VAD-FMK Improves Cryotolerance of in Vitro Derived Bovine Embryos

0 | May 26 2020

Maria Elena Pero et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibited cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential used as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. [Read the Full Post]

Caspase-3 Inhibitor Z-DEVD-FMK Enhances Retinal Ganglion Cell Survival and Vision Restoration After Rabbit Traumatic Optic Nerve Injury

565 | Apr 28 2020

Yuanyuan Liu et al. showed the caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans. [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]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

0 | Apr 11 2020

Davis RB et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease

661 | Apr 10 2020

Busch L et al. suggested that MALE might be associated with dual HTPR. [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]

Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis

0 | Apr 06 2020

Mancarella S et al. provided new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

722 | Mar 26 2020

Augello G et al. indicated their results offer hope for a new therapeutic opportunity in the treatment of HCC patients. [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]

An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring

430 | Mar 06 2020

Mohamed-Ahmed AHA et al. showed that Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery. [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]

Crenigacestat, a Selective NOTCH1 Inhibitor, Reduces Intrahepatic Cholangiocarcinoma Progression by Blocking VEGFA/DLL4/MMP13 Axis

1192 | Feb 23 2020

Serena Mancarella et al. developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition

462 | Feb 14 2020

Hong AL et al. identified a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome 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]

Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001

475 | Jan 28 2020

Shaw AT et al. showed the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. [Read the Full Post]

Daratumumab prevents programmed death ligand-1 expression on antigen-presenting cells in de novo multiple myeloma

455 | Jan 28 2020

Stocker N et al. suggested new mechanisms of action of Dara through depletion of pDC and prevention of PD-L1 upregulation expression on APC. Our finding provides new evidences for development of therapeutic strategies targeting both CD38 and PD-L1/PD-1 pathway in patients with MM. [Read the Full Post]

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

449 | Jan 18 2020

Wang YY et al. suggested that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells. [Read the Full Post]

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

0 | Jan 12 2020

Lawrence CP and Chow SC demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

Diacylglycerol kinase δ destabilizes serotonin transporter protein through the ubiquitin-proteasome system

539 | Jan 04 2020

Lu Q et al. provide novel insights into serotonergic system regulation and the pathophysiology/therapeutics of serotonin-/SERT-related diseases such as obsessive-compulsive disorder, depression, autism and schizophrenia. [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]

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]

Hypoxia-Induced Cleavage Of Soluble ephrinA1 From Cancer Cells Is Mediated By MMP-2 And Associates With Angiogenesis In Oral Squamous Cell Carcinoma

368 | Dec 04 2019

Ma TT et al suggested a possible novel mechanism that ephrinA1 secretion is mediated by HIF-1α/MMP-2 signaling cascade which may play pivotal roles in OSCC neovascularization in a paracrine manner. [Read the Full Post]

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

695 | Dec 02 2019

Pisklakova A et al. indicated that targeting Notch may be considered as a new strategy to be tested for MM therapy. [Read the Full Post]

An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer

609 | Nov 07 2019

Wang H et al. developed a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets. This approach is applicable to other oncogene driven cancers. [Read the Full Post]

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

0 | Nov 06 2019

Do Carmo H et al. indicated the caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. [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]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques

535 | Oct 20 2019

Laforge M et al. demonstrated that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS. [Read the Full Post]

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

626 | Oct 15 2019

Barreyro FJ et al. demonstrated that in a murine model of NASH, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in NASH. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

776 | 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]

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]

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

584 | Sep 25 2019

Holkova B et al. showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. [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]

Quantifying Risk Pathway Crosstalk Mediated by miRNA to Screen Precision drugs for Breast Cancer Patients

878 | 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]

Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

1938 | 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]

Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation

497 | Aug 25 2019

Zhang Y et al. identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

1667 | Aug 18 2019

Davis RB et al. showed that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial

687 | Aug 16 2019

Kogame N et al. found that after PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. [Read the Full Post]

Use of Antiplatelet Therapy/DAPT for Post-PCI Patients Undergoing Noncardiac Surgery

738 | Aug 14 2019

Banerjee S et al. present3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention. [Read the Full Post]

Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer

447 | Jul 29 2019

Gross MI et al. provided a strong rationale for the clinical investigation of CB-839 as a targeted therapeutic in patients with TNBC and other glutamine-dependent tumors. [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]

Phenotypic Drug Screening for Dysferlinopathy Using Patient-Derived Induced Pluripotent Stem Cells

588 | Jul 24 2019

Kokubu Y et al. suggested that increasing the amount of misfolded dysferlin using small molecules could represent an effective future clinical treatment for dysferlinopathy. Stem Cells Translational Medicine2019. [Read the Full Post]

Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of in vitro derived bovine embryos

0 | Jul 22 2019

Pero ME et al. indicated the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibits cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential use as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. Further studies are though needed to evaluate the effect of Z-VAD-FMK on post-transfer embryo development before considering a commercial application. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

752 | Jul 05 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [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]

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

754 | 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]

MMP14-Containing Exosomes Cleave VEGFR1 and Promote VEGFA-Induced Migration and Proliferation of Vascular Endothelial Cells

543 | Jun 16 2019

Han KY et al. showed that MMP14-containing exosomes may be involved in the regulation of corneal neovascularization through degradation of VEGFR1 and VEGFA-induced endothelial cell proliferation and migration. [Read the Full Post]

Combination of Emricasan with Ponatinib Synergistically Reduces Ischemia/Reperfusion Injury in Rat Brain Through Simultaneous Prevention of Apoptosis and Necroptosis

542 | Jun 10 2019

Tian J et al. concluded that combination of emricasan with ponatinib could synergistically reduce I/R injury in rat brain through simultaneous prevention of apoptosis and necroptosis. Our findings might lay a basis on extension of the clinical indications for emricasan and ponatinib in treating ischemic stroke. [Read the Full Post]

Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of in vitro derived bovine embryos

981 | May 17 2019

Pero ME et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibits cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential use as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. [Read the Full Post]

Molecular detection of Hsp90 inhibitor suppressing PCV2 replication in host cells

639 | May 13 2019

Liu J et al. highlighted the importance of cellular proteins during PCV2 infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies. [Read the Full Post]

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

700 | May 04 2019

Lawrence CP et al. demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

740 | Apr 22 2019

Do Carmo H et al. indicated the caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. [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]

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]

Memantine and Q-VD-OPh Treatments in Experimental Spinal Cord Injury: Combined Inhibition of Necrosis and Apoptosis

622 | Apr 05 2019

Aydoseli A et al showed that combined use of memantine and Q-VD-OPh provides better histological and clinical results. The combined inhibition of the two major pathways, necrosis and apoptosis, needs to be further assessed with in-vivo or in-vitro studies. [Read the Full Post]

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

784 | Mar 17 2019

Moreau P et al. showed the addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.). [Read the Full Post]

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA

753 | Mar 17 2019

Wei X et al. indicated that NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC. [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]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

2745 | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells

563 | Feb 03 2019

Thompson RM et al. suggested that the acquisition of PI resistance involves adaptations in cellular bioenergetics, supporting the combination of CB-839 with Crflz for the treatment of refractory MM. [Read the Full Post]

Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells

592 | Jan 16 2019

Choi B et al. suggested that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression. [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]

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]

Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

0 | Dec 25 2018

Vinholt PJ et al. indicated that dabigatran exclusively inhibits thrombin-induced platelet activation and aggregation with a dose-dependent response. Platelet stimulation with other agonists was not affected by dabigatran. [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]

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]

Methods for 20S Immunoproteasome and 20S Constitutive Proteasome Determination Based on SPRI Biosensors

788 | Dec 06 2018

Anna S et al. indicated 20Si and 20Sc were determined in blood plasma samples from healthy donors and patients with acute leukemia. In the case of these patients 20Si was the major component, and its level was more than one order of magnitude higher than in the healthy donors. [Read the Full Post]

Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction

816 | Dec 02 2018

Wang L et al. suggested that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI. [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

1937 | 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]

Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

0 | Nov 08 2018

Areeb Z, et al. indicated carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme. [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]

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]

Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons

938 | Oct 10 2018

Laidlaw SM et al. found TNF to have antiviral effects independently of, as well as in combination with, IFNs. TNF inhibits HCV infection despite increased HCV envelope glycoprotein-mediated infection of liver cells. These findings contradict those from other studies, which have reported that TNF blocks signal transduction in response to IFNs. The destructive inflammatory effects of TNF must be considered along with its antiviral effects. [Read the Full Post]

PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally

0 | Oct 09 2018

Graci JD et al. identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region. [Read the Full Post]

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis

1296 | Sep 11 2018

Wu Y et al. revealed a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC. [Read the Full Post]

Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway

1287 | Sep 11 2018

Barnawi R et al. demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. [Read the Full Post]

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus

882 | Aug 16 2018

Pérez-Hernández M et al. provided evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

0 | Aug 16 2018

Tao YF et al. may provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses

1232 | Aug 13 2018

Yi G et al. showed that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation. [Read the Full Post]

A profiling study of a newly developed HCVcc strain PR63cc's sensitivity to direct-acting antivirals

1229 | Aug 12 2018

Tao W et al. showed that PR63cc was more resistant than JFH1 to the asunaprevir/daclatasvir combination treatment. In summary, our study systemically analyzed the DAA sensitivity of a new HCVcc strain and identified critical RAVs. These results are not only important for monitoring the emergence of drug-resistant mutations of current DAA therapies, but also valuable for developing next-generation DAAs. [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]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

1547 | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia

967 | Aug 06 2018

Wang Q et al. found that Combined treatment with CFZ and z-VAD-fmk early in the development of cachexia was associated with signs of less proteolysis and apoptosis and less severe cachexia in a mouse model of cancer-induced cachexia. [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]

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

1277 | 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]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

1389 | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

1444 | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

1393 | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

1494 | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [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]

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability

645 | Jul 09 2018

Qian YW et al. elucidated a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. [Read the Full Post]

A simple and cost-saving phenotypic drug susceptibility testing of HIV-1

1502 | Jul 05 2018

Weng Y et al. provided a useful tool for interpreting meaningful genotypic mutations and guiding tailored antiviral treatment of HIV/AIDS in clinical practice. [Read the Full Post]

Dissecting the molecular mechanisms that impair stress granule formation in aging cells

1188 | Jul 04 2018

Moujaber O et al. demonstrated that the loss of CReP correlated with the aging-related hyperphosphorylation of eIF2α. Together, we have identified significant changes in the stress response of aging cells and provide mechanistic insights. Based on our work, we propose that the decline in SG formation can provide a new biomarker to evaluate cellular aging. [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]

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]

Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

1258 | Jun 12 2018

Sanchez G et al. suggested that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. [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]

ADAMTS13 and 15 are not regulated by the full length and N-terminal domain forms of TIMP-1, -2, -3 and -4

808 | Jun 04 2018

Guo C et al. indicated that TIMPs are not the regulators of these two ADAMTS proteinases. [Read the Full Post]

Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue

3232 | May 16 2018

Liu Z et al. revealed a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. [Read the Full Post]

Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis

1056 | May 16 2018

Wang Y et al. unraveled the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases. [Read the Full Post]

HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells

1320 | May 13 2018

Cai Y et al. showed that combining OMT with an inhibitor of autophagy or HMGB1 may make OMT more effective in the treatment of human synovial sarcoma. [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]

Investigating proteasome inhibitors as potential adjunct therapies for experimental cerebral malaria

1059 | May 11 2018

Howland SW et al. reported here that bortezomib, which has been associated with neurological adverse events, accelerated death in ECM-infected mice. [Read the Full Post]

COPS5 amplification and overexpression confers tamoxifen-resistance in ERα-positive breast cancer by degradation of NCoR

1922 | Apr 14 2018

Lu R et al. demonstrated that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine-resistant breast cancer patients. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response.

1086 | Mar 16 2018

Zhao Z et al. found that the HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [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]

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

3216 | Feb 26 2018

Schaale K et al. indicated in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Feb 23 2018

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs [Read the Full Post]

Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

948 | Feb 18 2018

Vinholt PJ et al. found dabigatran exclusively inhibits thrombin-induced platelet activation and aggregation with a dose-dependent response. [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]

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]

Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis

1422 | Jan 12 2018

Gong Z et al. offered a mechanistic basis to ameliorate cholestatic liver fibrosis by targeting inflammasome activation. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

1973 | Jan 05 2018

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 GSK126 in patients with MM may be warranted. [Read the Full Post]

Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib

1009 | Jan 05 2018

Law S et al. determined and compared the structures of inhibitor-free mouse CatK (mCatK), hCatK and ODN bound to hCatK. [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]

PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally.

1514 | Dec 29 2017

Graci JD et al. identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region. [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]

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]

Matrine induces Akt/mTOR signalling inhibition-mediated autophagy and apoptosis in acute myeloid leukaemia cells

1258 | Dec 20 2017

Wu J et al. indicated that matrine exerts antitumour effect through apoptosis and autophagy, and the latter one might be a potential therapeutic strategy for AML. [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]

Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells.

1445 | Dec 16 2017

Wang S et al. found that the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer. [Read the Full Post]

E platinum, a newly synthesized platinum compound, induces apoptosis through ROS-triggered ER stress in gastric carcinoma cells

1474 | Dec 09 2017

Wang X et al. indicated that E Platinum may be a potential and effective treatment for gastric cancer in clinical. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

1640 | Nov 22 2017

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

1523 | Nov 21 2017

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Nov 18 2017

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides). [Read the Full Post]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

2331 | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [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]

Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling

972 | Sep 25 2017

Guo L et al. showed that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition. [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]

Role of BmDredd during Apoptosis of Silk Gland in Silkworm, Bombyx mori

1549 | Sep 04 2017

Chen RT et al. suggested that BmDredd plays a critical role in SG apoptosis. [Read the Full Post]

The Role of the Active Oxygen Produced from Gp91phox NADPH Oxidase on the Newborn Weight of Mouse Pups

1586 | Sep 03 2017

Keiichi Hiramoto et al. indicated that gp91phox NADPH oxidase produces ROS during graviditas. The ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1, thereby finally inducing IGF-1. Because the newborn weight is determined by IGF-1, gp91phox appears to be important for promoting fetal growth during graviditas. [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]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Aug 11 2017

Wu D, et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

2026 | Aug 09 2017

Cayrol F et al. indicated the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Analysis of a cAMP regulated coactivator family reveals an alternative phosphorylation motif for AMPK family members

1617 | Aug 08 2017

Sonntag T et al. suggested that the regulation of cellular targets by AMPK family members is more extensive than previously appreciated. [Read the Full Post]

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

2312 | Jul 25 2017

Bui QT et al. concluded Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer. [Read the Full Post]

Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells

2311 | Jul 25 2017

Wei J et al. demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial 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]

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]

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]

NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling.

1803 | Jun 08 2017

Wang Z et al. proposed that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

0 | Jun 07 2017

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate

0 | Jun 06 2017

Hoffman M et al. found that a cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. [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]

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]

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]

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]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling.

1776 | May 02 2017

Cheng M et al reported that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [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]

Tetrachlorobenzoquinone induces Nrf2 activation via rapid Bach1 nuclear export/ubiquitination and JNK-P62 signaling

1690 | Apr 21 2017

Su C et al. found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling. [Read the Full Post]

Reversal of Dabigatran Effects in Models of Thrombin Generation and Hemostasis by Factor VIIa and Prothrombin Complex Concentrate

0 | Mar 25 2017

Hoffman M et al suggested that a cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. Enhancing the rate of thrombin generation and peak thrombin level appear to correlate best with hemostasis in vivo. The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal. [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]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

3483 | 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]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Mar 04 2017

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response

1877 | Feb 25 2017

The HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Solitary inhibition of the breast cancer resistance protein (BCRP) efflux transporter results in a clinically significant drug-drug interaction with rosuvastatin by causing up to a two-fold increase in statin exposure

2580 | Feb 25 2017

Elsby R, et al.'s result shows that solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant statin dose adjustment in clinical practice [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [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]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3252 | Feb 06 2017

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate

2817 | Jan 30 2017

The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal. [Read the Full Post]

Understanding the molecular mechanism of host-based statin resistance in hepatitis C virus replicon containing cells

2307 | Jan 28 2017

Delang L et al. demonstrated that statin resistance in HCV replicon containing hepatoma cells is conferred by changes in the cellular environment. [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]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Jan 21 2017

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Solitary Inhibition of the Breast Cancer Resistance Protein Efflux Transporter Results in a Clinically Significant Drug-Drug Interaction with Rosuvastatin by Causing up to a 2-Fold Increase in Statin Exposure

1356 | Jan 13 2017

Elsby R et al. found that solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant statin dose adjustment in clinical practice. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

4431 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

2599 | Dec 31 2016

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3703 | Dec 29 2016

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [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

2938 | 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]

Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis

1855 | Dec 17 2016

Lu YX et al. suggested that nafamostat mesilate, a relatively non-toxic drug that targets NF-κB and Erk, may, in combination with oxaliplatin, represent a novel therapeutic strategy for CRC treatment. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

2662 | Dec 10 2016

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [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]

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]

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests

2884 | 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]

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]

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]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

2818 | 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]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

2214 | Sep 28 2016

Cheng M et al. revealed a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [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]

ERK induces degradation of tumor suppressor FBW7 in pancreatic cancer

7475 | Mar 18 2015

Ji et al. demonstrated a correlation between low expression of FBW7 and ERK activation in pancreatic cancer. [Read the Full Post]

MiR-146-NF-κB pathway is a key axis in the regulation of FOXP3-deficient prostate cancers

4106 | Mar 12 2015

Liu et al. from University of Alabama at Birmingham reveal FOXP3-microRNA-146(miR-146)-NF-κB axis as a critical signaling pathway in regulating the survival of prostate cancer cells both in vitro and in vivo. [Read the Full Post]

RIP1, a novel oncogenic driver in melanoma

5039 | Mar 06 2015

u et al. found that RIP1 plays a role as an oncogenic driver in human melanoma. [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]

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]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10501 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Proteasome inhibitor salvages messense mutated dysferlin in muscular dystrophy patients

3972 | Feb 09 2015

Azakir et al. demonstrated proteasome inhibitor is able to increase the expression of messense mutated dyferlin, and restores the membrane resealing capacity of myoblasts. [Read the Full Post]

Suppressing HER3 signaling by interfering with its Sec61-dependent contranlational translocation

3973 | Feb 03 2015

Ruiz-Saenz et al. demonstrated a novel approach specifically reduces HER3 expression. [Read the Full Post]

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

6517 | Jan 30 2015

Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. [Read the Full Post]

The inhibition of class I histone deacetylases by butyrate can suppress acute gout arthritis

5118 | Jan 22 2015

Cleophas et al. found high concentration of short-chain fatty acid butyrate provides anti-inflammatory effect by inhibiting of histone deacetylases (HDACs) in acute gout arthritis. [Read the Full Post]

Butyrate acts as an suppressor against colonic tumor in gnotobiotic mouse models

5383 | Jan 19 2015

Donohoe et al. demonstrated dietary fiber suppress tumor progress in a microbiota- and butyrate-dependent manner. [Read the Full Post]

Snail also acts as a transactivator for the expression of tumor-associated cytokines

6837 | Jan 16 2015

Hsu et al. demonstrated the underlying mechanism of Snail-mediated target gene transactivation, and also identified several target genes. [Read the Full Post]

The mechanism of action of new antitumor drug FL118

4143 | Dec 25 2014

Recently, Ling et al. demonstrated the mechanism of FL118 antitumor action. The drug suppress tumor growth by promotion of MdmX degradation and consequent stimulation of p53 signaling. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

10058 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

7404 | Dec 09 2014

Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. [Read the Full Post]

Hippo signaling mediates hypoxia tumorgenesis via SIAH2

4400 | Dec 05 2014

Ma et al. gives a insight into the mechanism of Hippo signaling by investigating the pathway deactivation induced by hypoxia. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

8720 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Notch signaling acts as a key regulator in generation of neurons from neural precursor cells

5693 | Oct 23 2014

Notch signaling plays a central role before asymmetric division and in the fate of Drosophila melanogaster neural precursor cells. It also acts as a critical factor in Numb distribution in neural precursor cells before cleavage. [Read the Full Post]

The effect of panobinostat on HIV latency disruption in a phase 1/2 clinical trial

5828 | Oct 22 2014

Rasmussen et al. found panobinostat, a histone deacetylase inhibitor, has the ability to activate infected cells from HIV latency. They also tested the safety of this strategy on phase 1/2 clinical trial. The effect of panobinostat treatment was not significant in reducing the number of latently infected cells. However, panobinostat effectively disrupt HIV latency in vivo. [Read the Full Post]

Not all DUBs are equal

3964 | Mar 21 2014

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

AGI5198 is the first highly potent and selective mutant IDH1 inhibitor

3628 | Mar 07 2014

AGI-5198, potently inhibits mutant IDH1 (R132H-IDH1 and R132C-IDH1), but not wildtype IDH1 (IC50 > 100 μM) or any of IDH2 isoforms (R140Q, R172K, wildtype) (IC50 > 100 μM) [Read the Full Post]

PCI34051 is a potent histone deacetylase 8 inhibitor

4392 | Mar 06 2014

PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM. It has greater than 200-fold selectivity over HDAC1 and 6. [Read the Full Post]

PCI 24781 is a broad spectrum hydroxamic acid based inhibitor of HDAC

4287 | Feb 25 2014

HDAC activity is measured using a continuous trypsin-coupled assay. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials

3758 | Feb 19 2014

MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. [Read the Full Post]

RO4929097 is a small molecule gamma secretase inhibitor

3661 | Feb 13 2014

RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. [Read the Full Post]

SB939 is a novel histone deacetylase inhibitor with improved

4434 | Feb 11 2014

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans

3331 | Jan 26 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Nutlin 3 is a cis imidazoline analog

4409 | Jan 26 2014

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor undergoing clinical trials

4419 | Jan 22 2014

MS-275 shows inhibitory to HDACs by 2-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor

4283 | Jan 21 2014

MS-275 shows inhibitory to HDACs by 2'-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials as an oral preparation

3210 | Jan 14 2014

MLN9708 immediately hydrolyzed to MLN2238, the biologically active form, on exposure to aqueous solutions or plasma. [Read the Full Post]

Bortezomib is a highly selective reversible inhibitor of the 26S proteasome

3272 | Jan 09 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

SB939 is a novel histone deacetylas inhibitor with improved

4326 | Dec 23 2013

SB939 is a potent pan-HDAC inhibitor with IC50 of 40-140 nM with exception for HDAC6. It has no activity against the class III isoenzyme SIRT I. [Read the Full Post]

Tipifarnib is a farnesyltransferase inhibitor

2911 | Dec 18 2013

Tipifarnib (R115777) is a potent and specific farnesyltransferase (FTase) inhibitor with IC50 of 0.6 nM, its anti-proliferative effects are most prominent in H-ras or N-ras mutant cells. [Read the Full Post]

Givinostat is a histone deacetylase inhibitor with potential

4040 | Dec 17 2013

Givinostat (ITF2357) is a potent HDAC inhibitor for HDAC2, HDAC1B and HDAC1A with IC50 of 10 nM, 7.5 nM and 16 nM. [Read the Full Post]

Bortezomib is the first clinically approved proteasome inhibitor for treating multiple human malignancies

3308 | Dec 16 2013

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Nutlin 3 inhibits the interaction between the proteins p53 and MDM2

4218 | Nov 29 2013

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor

3445 | Nov 26 2013

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

CUDC 101 is a potent inhibitor of histone deacetylase

4107 | Nov 25 2013

CUDC-101 is a potent multi-targeted inhibitor against HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, and inhibits class I/II HDACs, but not class III, Sir-type HDACs. [Read the Full Post]

BMS 790052 is the most potent hepatitis C virus inhibitor

4523 | Nov 13 2013

BMS-790052 is a highly selective inhibitor of HCV NS5A with EC50 of 9-50 pM, for a broad range of HCV replicon genotypes and the JFH-1 genotype 2a infectious virus in cell culture. Phase 3. [Read the Full Post]

FK866 has been shown to induce apoptosis by non competitive

3210 | Nov 12 2013

APO866 effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase) with IC50 of 0.09 nM. Phase 1/2. [Read the Full Post]

SB939 is a pan histone deacetylase inhibitor binding

4222 | Nov 04 2013

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

Trichostatin A is an organic compound that serves as an antifungal antibiotic

3958 | Oct 25 2013

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM – HDAC8 is the only known member of the HDAC-family that is not affected by TSA. [Read the Full Post]

Semagacestat was compared with placebo in more than 2600 patients

3397 | Oct 21 2013

Semagacestat reduces the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably overexpressing human wild-type APP into the culture medium [Read the Full Post]

Nutlin3 inhibits the MDM2 p53 interaction and activates p5

4058 | Sep 26 2013

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

MS275 strongly inhibits HDAC1 and HDAC3 with IC50

3913 | Aug 29 2013

MS-275 exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. [Read the Full Post]

PD168393 is a strongly effective EGFR inhibitors

3415 | Jul 18 2013

PD 168393 is docked into the ATP binding pocket of EGFR TK. PD168393 completely suppresses EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure, with continous suppression even after 8 hr in compound-free medium. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

3158 | Jun 20 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. [Read the Full Post]

Learn about the prescription medication Methazolamide

2935 | May 26 2013

Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. [Read the Full Post]

Effects of oral administration of methazolamide on intraocular pressure

2884 | May 22 2013

In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics [Read the Full Post]

LY2484595 is one of two CETP inhibitors currently being evaluated

2911 | May 02 2013

LY2484595 results in 98.4%, 98.6%, and 18.4% inhibition of CETP activity at 4 hours, 8 hours and 24 hours post dose respectively in human ApoAI and CETP double transgenic mice. [Read the Full Post]

Tubastatin A was substantially more selective than the known HDAC6 inhibitor

4132 | Apr 28 2013

Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

3848 | Apr 22 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. MG-132 induces neurite outgrowth in PC12 cells at an optimal concentration of 20 nM. [Read the Full Post]

PS341 was tested in a small Phase I clinical trial on patients with multiple myeloma cancer

2818 | Mar 25 2013

PS-341 is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma[1] and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. [Read the Full Post]

Telaprevir is an associate of a class of antiviral drugs

4619 | Mar 21 2013

Telaprevir is an associate of a class of antiviral drugs called protease inhibitors. Especially, telaprevir prevents the hepatitis C viral enzyme NS3.4A serine protease. Telaprevir is just indicated for use against hepatitis d genotype 1 viral infections and hasnt been which can have an impact on or being protected when employed for other genotypes of the herpes virus. The standard therapy of ribavirin and pegylated interferon is less successful on genotype 1 and a welcome addition is offered by telaprevir to the treatment of this genotype. [Read the Full Post]

Vorinostat is a member of a larger class of compounds that inhibit histone deacetylases

4052 | Mar 06 2013

A total of 155 children were screened for enrollment in the study, with 110 children being excluded on the basis of the enrollment criteria. The predominant reasons for exclusion were based on either the age or the weight criterion. Forty-five Vorinostat children meeting enrollment criteria for the PK substudy were enrolled: 23 in the AL arm and 22 in the AQ-AS arm. [Read the Full Post]

MDV3100 is an androgen receptor antagonist

2601 | Jan 15 2013

Increased protein levels and kinase activities of Src family kinases have been observed in a wide diversity of human cancers, including melanoma, breast, ovarian, and lung cancer . The prototype SFK is c-Src, MDV3100 which is a protein tyrosine kinase from which the oncogenic viral Src is derived . [Read the Full Post]

DPP 4 is regulated transcriptionally RGS4

3155 | Dec 04 2012

[Read the Full Post]

Gamma Secretase were grown in 5 ml of medium

5367 | Nov 28 2012

The cells were pelleted by centrifugation, the medium was Gamma Secretase removed with the drug, and the cells were washed washed with sterile PBS and centrifuged again. [Read the Full Post]

Telaprevir has very poor penetration of the blood brain

5546 | Nov 15 2012

The principal metabolic fate of loperamide in humans involves oxidative N dealkylation to N demethyl loperamide as the principal metabolite. In human liver microsomes, cytochrome P450 3A4 appears to be the major isozyme responsible for loperamide metabolism, with minor contributions from CYP2B6 [Read the Full Post]

DPP-4 of cisplatin ECCC involved downregulate

3635 | Nov 02 2012

Th Rho kinase and PI-3-kinase in ECCC completely yet Constantly described. In this study we have tried to determine whether to f HA and CD44 on Rho kinase and PI-3-kinase signaling progression ECCC Interact rdern [Read the Full Post]

HDAC is also shown to occur in an inhibitor

4397 | Oct 24 2012

These include KIT, RET, STK11 LKB1. These are all known cancer associated kinases that have dysregulated signaling in various human cancers, including GIST and hematological malignancies, papillary thyroid cancer and lung cancer [Read the Full Post]

BMS-790052 A Tr droplets With twice as many cells pressed

4525 | Oct 23 2012

BMS-790052 A Tr droplets With twice as many cells pressed agA Tr droplets, With twice as many cells pressed against the heart tee h Here cAMP concentration against each other, the proportion of droplets tears reported a positive response [Read the Full Post]

VORINOSTAT: A HYDROXAMIC ACID

4997 | Sep 10 2012

VORINOSTAT OR SAHA (SUBEROYLANILIDE HYDROXAMIC ACID): Histone deacetylase inhibitors or HDACi perform functions in the regulation of gene expression, cell cycle arrest, apoptosis stimulation in cancer cells and variation of different pathways in cancer cells such as cellular proliferation due to hyperacetylating the histone proteins. HDAC inhibitors are one of the leading approach for the treatment of cancers and tumors and among these inhibitors Vorinostat SAHA is the important one. This inhibitor is found to have strong anti-oncogenic properties and the Vorinostat structure contains a molecules having hydroxamic acid. For both classes of HDAC inhibitors that is class I and II the Vorinostat IC50 is about 50nM. The solubility of Vorinostat is around 2mg/ml in ethanol where it is highly soluble in DMSO in which 65mg/ml is Vorinostat solubility but it is poorly soluble in water. Stability of Vorinostat is of about 24 months when stored at -20 ºC. One can purchase Vorinostat for research purpose from any of the Vorinostat supplier by spending Vorinostat price that is $26 for a vial of 100mg however the prices are variably depending upon purity of the salt and supplier. Amongst different HDAC inhibitors the first FDA approved such inhibitor is Vorinostat HDAC inhibitor for the treatment of T-cell lymphoma. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS BEYOND CANCER TREATMENT

4576 | Sep 02 2012

EPIGENEITIC MODULATION AND HDAC INHIBITORS In cellular genome a major part comprises of histone proteins and these proteins upon addition of acetyle group perform some of the most important cellular pathways are controlled by these proteins, these pathways include cell growth and proliferation and programmed cell death. When the acetyle group is detached from histones the process of apoptosis starts because most of the genetic expression of some vital proteins is ceased due to deacetylation and in addition to this the DNA condensation is also increased due to increased DNA binding capacity. It has been noticed that during neurodegenerative diseases the process of deacetylation is disturbed which leads to different types of cancers and tumors which is characterized by uncontrolled cell proliferation. These studies encouraged the discoveries of HDAC inhibitors and also enlighten the HDAC inhibition process. In preclinical and clinical evaluations HDAC inhibitions have been applied which leads to the successful and detailed use of this process by good number of researchers. Various activity assays are available for the estimation of HDACs levels. Kits are available for such assays however these can also be performed manually in the lab. HDAC inhibitors analysis can also be done by a nonisotopic assay which is microplate reader compatible and test for robotic screening and compound profiling is also available or another assay which is suitable for high throughput screening. [Read the Full Post]

BORTEZOMIB: AN INHIBITOR OF PROTEASOMAL DEGRADATION

2875 | Aug 28 2012

BORTEZOMIB Proteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g.,green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

HDAC INHIBITORS AGAINST TOMORS

4763 | Aug 22 2012

HDAC INHIBITION: A SOURCE OF EPIGENETIC MODULATION Histone acetylation is an essential process in functions like cell growth and cellular death by causing the inhibition of transcription of proteins caused by removal of the acetyl groups from the histone proteins, as a result of which the binding of DNA is increased, causing it to be condensed. A disturbance in this phenomenon leads to an uncontrolled growth of the cells that leads to the production of tumors and neurodegenerative diseases as well. HDAC inhibition is performed to treat various forms of tumors by using HDAC-2 inhibitors. Different successful studies at various levels have elucidated the mechanism of action of HDAC inhibitors leading to their enormous applications in various preclinical and clinical trials. The levels of HDAC inhibitors can be assessed by the use of different sort of assays specially developed for this reason. These chemical assays can be performed in laboratory by using various kits. The researchers can perform nonisotopic HDAC inhibitor and microplate reader compatible assay and the one for the robotic screening and compound profiling. In addition to it a simple flourogenic assay can also be used for the high-throughput screening process. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

4513 | Aug 15 2012

HDAC INHIBITION AND EPIGENETIC MODULATION An important process; histone acetylation is related to cellular functions for example cell death and cell growth stimulating the protein transcription inhibition by removing the acetyl groups from the related proteins hence causing the increase in DNA binding and making it more condensed. Any disturbance in this process leads to the uncontrolled cellular growth that further leads to the tumor production and also the neurodegenerative diseases. Histone deacetylase inhibition is carried out for the treatment of different types of tumors by using the HDAC-6 inhibitors. Various successful studies at different levels have exhibited the mode of action of histone deacetylase inhibitors further leading to their vast area of applications in different clinical and pre-clinical studies. The HDAC inhibitors levels can be analyzed by using various types of assays specifically developed for this purpose. These assays can be carried out in the labs through different kits. Researchers can perform microplate reader compatible assay and the nonisotopic HDAC inhibitor assay and also the one for compound profiling and robotic screening. In addition to this simple flourogenic assay may also be carried out for the process of high-throughput screening. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

4479 | Aug 01 2012

EPIGENETIC MODULATION VIA HDAC INHIBITION: Histones acetylation is vital process in the functions like cellular growth and cell death by inhibiting the transcription of proteins which is caused by the removal of acetyl groups from histones as a result the DNA binding increases and DNA is condensed. When this process is disturbed it leads to uncontrolled growth of cells leading to the formation of cancers and also neurodegenerative diseases. HDAC inhibition for the treatment of cancer comes by the use of HDAC inhibitors. Successful studies elucidating mechanisms of HDAC inhibitors led to their vast applications in different clinical and preclinical studies. HDAC levels can be assessed by using various assays developed for this purpose. These assays can be performed in lab by the help of kits. Researchers can perform microplate reader compatible and nonisotopic HDAC inhibitor assay and one for compound profiling and robotic screening and in addition to this simply a flourogenic assay can be performed for high-throughput screening. [Read the Full Post]

INHIBITORS OF HISTONE DEACETYLASE

3618 | Jul 13 2012

HDAC INHIBITORS AND EPIGENEITIC VARIATION Different functions of the cell like apoptosis, cell multiplication and growth is controlled by genes present in cell histone proteins comprise the large portion these genes. These histone proteins act when they are being acetylated. When these histone proteins get deacetylated they trigger apoptosis because translation of vital proteins gets stopped when they are being deacetylated and also binding capability of DNA is increased due its condensation. Studies showed that in neurodegenerative diseases deacetylation process is seemed blocked which ultimately gave rise to unchecked growth of cells which is characteristic of various kinds of carcinomas and malignancies. These findings forced scientists to discover HDAC inhibitors brought into light the process of HDAC inhibition. Quite large number of researchers described in detail the process of inhibition by administering HDAC inhibitors in clinical as well as pre-clinical trials. Different activity estimation assays are present to assess levels of HDACs. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEASOMAL AGENT

4089 | Jul 01 2012

BORTEZOMIB: INTRODUCTION In cell among the tiny organelles proteasomes are the foremost vital ones. They play necessary role in the correct regulation of the cell cycle by removing the proteins that don't seem to be necessary for cell. In cancer cell it rarely happens that the proteins which are involved in the controlling the dysregulated growth of the cells are excised by proteasomes. A promising target for the therapy of cancer is to inhibit proteasomes so that the uncontrolled growth is inhibited. A variety of compounds were typically used for cancer therapy that inhibits proteasomes. Among them EGCG additionally referred to as Epigallocatechin-3-gallate, Disulfiram and Salinosporamide-A that are present in green tea were used. The primary inhibitor of proteasomes that got approved to enter clinical trials for cancer therapy is Bortezomib. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – CANCERS AND BEYOND

4702 | Jun 26 2012

HDAC INHIBITIORS AND EPIGENEITIC MODULATION: Histone proteins are major part of cellular genome and acetylation of these proteins plays a mile stone role in some of the most important cellular mechanisms such as growth of cell and cell death by apoptosis. The process which controls apoptosis process is carried out by checking the gene transcription of different important proteins by removing acetyl groups from histones, this deacetylation leads to condensation of DNA due to increasing capacity of DNA binding. In neurodegenerative diseases this mechanism of deacetylation goes wrong leading to various types of cancers in which cell proliferation is uncontrolled. This problem leads to the HDAC inhibitor pathway and smoothes the process of HDAC inhibition. HDAC inhibitions have been employed in preclinical and clinical studies due to which extensive and successful use of this process is targeted by many researchers. HDACs levels estimation has been developed by different activity assays. These assays are carried out by manually in the research lab or by kit methods. A nonisotopic assay that is microplate reader compatible can also be performed by researchers for the analysis of HDAC inhibitors, an appropriate test for compound profiling and robotic screening or a suitable fluorescence assay for high-throughput screening. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEIN DEGRADATION AGENT

5188 | Jun 20 2012

BORTEZOMIB Proteasomes belong to one of the important small organelles present in cell. Cell cycle is regulated by these proteasomes as they remove any unnecessary protein from cell. Usually during the cancer state the proteins which inhibit uncontrolled cell development of cancer are chopped down by these proteasomes. To stop chop these abnormal proteins properly inhibition of proteasomes is necessary which offers a good target for cancer therapy. For cancer treatment a lot of various compounds are being employed that cause proteasomes inhibition for example e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib was entitled to be first inhibitor that got approval to enter clinical studies for treatment of cancer. [Read the Full Post]

BORTEZOMIB; INHIBITING PROTEIN DEGRADATION

4132 | May 17 2012

BORTEZOMIB Poteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

VORINOSTAT: THE FAMOUS HYDROXAMIC ACID

4019 | May 15 2012

SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) OR VORINOSTAT: Functions of HDACi (HDAC inhibitors) is to regulate the gene expression, induction of cell cycle arrest, stimulate apoptosis in cancer cells and modulation of various pathways in tumor cells for example cell proliferation, by hyperacetylating the histone proteins. Due to possessing these abilities, HDAC inhibitors are being used as a very valuable chemotherapeutic anti-cancer agents and SAHA or Vorinostat SAHA is important among them [1]. Vorinostat has found to be possessing strong anti-cancer properties [2] and Vorinostat structure reveals that this molecule is a derivative of hydroxamic acid. For HDAC inhibitors class I and HDACi class II Vorinostat IC50 is found to be near 50 nM. Vorinostat is soluble is ethanol up to 2 mg/ml and in DMSO 65 mg/ml but Vorinostat solubility is found to be very poor in water. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3807 | May 06 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. [Read the Full Post]

BORTEZOMIB – PROTEASOMAL INHIBITOR

3816 | Apr 26 2012

BORTEZOMIB: One of the most important categories of enzymes in the cell is the protein degrading enzymes called as proteosomes. They degrade all types of un-wanted proteins in the cells hence can regulate some important pathways in the cells like gene expression and cell cycle. The compounds which obstruct the activity of these enzymes play an important role in process of inhibition of degradation of cancer inhibiting proteins. Due to these properties proteosome inhibiting molecules like EGCG (Epigallocatechin-3-gallate) known as green tea as well, Disulfiram and Salinosporamide-A have been found to use for treatment of cancer. The first approved proteosomal inhibiting drug for clinical studies is Bortezomib and it is a very famous inhibitor of this class of enzymes. [Read the Full Post]

VORINOSTAT – AN ANTI HISTONE MODIFYING AGENT

3988 | Apr 17 2012

CHROMATIN REMODELLING INHIBITION IN CANCER THERAPY Histone modification is a very important phenomenon regarding regulation of expression of genes. Acetylation and deacetylation of histones in attached to the genetic material i.e., DNA is done with the help of specific proteins, therefore, in order to inhibit or stimulate the expression of specific genes histone tail modifying proteins can be modified. Histone deacetylating Complexes (HDACs) are one of these modifying proteins which inhibit the expression of some genes by de-acetylating them. Inhibiting these proteins may function in the modulation of gene expression by hyperacetylating them. HDAC inhibitors hence modulate the aberrant expression of genes in cancerous cells. They may inhibit cell division, arrest cell cycle or stimulate apoptosis. A lot of research is being done on different types of HDAC inhibitors in order to use them as anti-cancer therapeutics. Vorinostat is one of such HDAC inhibitors. It is also known as Suberoylanilide Hydroxamic Acid (SAHA). [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3562 | Apr 16 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. Various assays for HDACs have been developed that are used for the analysis of HDAC levels. [Read the Full Post]

BORTEZOMIB – A PROTEASOME INHIBITOR

3447 | Apr 10 2012

BORTEZOMIB: There are different enzymes are present in the cell and amongst these enzymes Proteasomes are large enzymes which play function of degrading un-wanted proteins of cells, therefore these enzymes regulate some of the most important pathways including cell cycle and genetic expression. Those compounds which hinder the actions of these proteasomes play important functions in the process of inhibiting the degradation of tumor inhibiting proteins. Because of these properties the proteasome inhibitors such as EGCG (Epigallocatechin-3-gallate) also known as green tea, Salinosporamide-A and Disulfiram have been applied for cancer treatment. Bortezomib is the first approved proteasome inhibitor for clinical trials; this is the most famous inhibitor of this category. [Read the Full Post]

PANOBINOSTAT

5618 | Mar 19 2012

Introduction: Inhibition of HDAC Of the 18 isoforms of the histone deacetylase enzyme the class one and class two proteins are the most frequently found to be over expressed in tumor tissue. The activity of the HDAC enzyme is to remove an acetyl group from a target protein which induces a conformational change so that further protein binding is induced or inhibited. The signal begins in the cellular cytosole and is transmitted to the nucleus. This signaling transfer results eventually in the regulation of a cellular growth activity, be that life or death! The class 1 & 2 enzymes function by binding their target protein to a binding domain which has a zinc atom as a functional part. This zinc atom catalysis the deacetylation process and is the target of inhibition for most known HDAC inhibitors. [Read the Full Post]

MS-275

4278 | Mar 19 2012

Introduction: HDAC inhibition In most cancerous tissue there exists an imbalance between regulatory pathways that came be exploited for chemotherapeutic activity. One of the pathways that exhibits such activity is the acetylation / de-acetylation pathway. The regulatory enzyme in this pathway is referred to as Histone deacetylase (HDAC) and it operates in balance with Histone acetyl transferase. The addition or removal of an acetyl group causes the protein conformational shape to change and this in turn triggers either an attraction or inhibition of a protein complex formation. This action sends a signal to the nucleus to being or stop growth actions. There are many HDAC enzymes located in the cellular cytosole or within the nucleus membrane and most activity is controlled by a zinc catalyst, one small group requires NAD+ to function instead. [Read the Full Post]

HDAC INHIBITORS – CANCERS AND BEYOND

3926 | Mar 19 2012

Introduction: Histone deacetylases Cellular growth is regulated via many different mechanisms in the mammalian species, depending on the mechanism or pathway that is triggered to what effect is seen in the body. One of these regulatory compounds is called histone deacetylase or abbreviated to HDAC. As it name indicates this enzymes function is to remove an acetyl group from a target, this can be either a protein or a non-protein molecule. The removal of the acetyl group results in a conformational change in the target protein that triggers further signaling down a “pathway” that results in the induction or inhibition of carious growth related activities in the cell. HDAC is not a single protein but exists in 18 different isoforms which are classified into four groups based on their activity and physical nature. Located in the nucleus are HDAC’s 1, 2, 3 & 8 responsible for mostly transcription activities. In the cytosole are the HDAC’s 4, 5, 7 & 9, these transmit signals between extracellular sources and the nucleus. HDAC 11 and HDAC’s 6 & 10 are located in between cytosole and nucleus, their function varies. [Read the Full Post]

CUDC -101: HDAC inhibitor

4189 | Mar 20 2012

Introduction: HDAC inhibition Regulation of the activity of the proteins that initiate and transmitted signals for the cellular growth or gene transcription is a vital process in the mammalian system. There are many different mechanisms that perform this task but o of the more significant is the addition or removal of an acetyl group. The enzyme’s most responsible for this activity is known as “Histone deacetylase” and “Histone transferase” or more commonly known as HDAC and HAT respectively. In a normal situation these two enzymes operate in a balanced mechanism but genetic aberrations can significantly affect this balance in one way or another. Most typically it is observed that the HDAC is over expressed or in a permanent “on” condition in most diseased states. With over 18 currently known isoforms of HDAC divided into class’s based on the mechanism of action this represents a major target for chemotherapeutic action To target HDAC an inhibitor should be able to interfere with the ligand – enzyme binding which occurs in the tyrosine kinase domain and two classes out of 4 HDAC’s require Zinc to catalyse the reaction. [Read the Full Post]

RO4929097 – CHECKS NOTCH SIGNALING IN CANCERS

5816 | Mar 20 2012

RO4929097: A GAMMA SECRETASE INHIBITOR: Among well known proteases Gamma secretase is one which is made up of various subunits. This is present in the membrane hence is a protein in membrane which is also capable of cleaving certain transmembrane proteins therefore also known as the intramembrane protease. In case of Alzheimer’s disease amyloid plaques are formed in brain, these plaques are resulted due to the amyloid beta peptide and these peptides are produced due to the action of gamma secretase, this is one of the well known examples of this protease. Presently, we are focusing on the important role of gamma secretase in the Notch protein processing. In case of many cancers and tumors this Notch protein signaling is found to be abnormal, therefore the arresting of this pathway can be an authentic way to get rid of abnormal cell growth. In the light of this idea a novel RO4929097 gamma secretase inhibitor is discovered. The inhibitory effect of this inhibitor has been confirmed by various methods like western blotting. [Read the Full Post]

TOSEDOSTAT: INHIBITING AMINOPEPTIDASES IN CANCERS

3452 | Mar 18 2012

AMINOPEPTIDASES AND THEIR INHIBITION: Aminopeptidases catalyze the cleavage of amino acids of proteins or peptide substrates. Such enzymes are zinc dependant and located throughout most mammalian tissue and in certain plant extracts. They are essential for many cellular maintenance functions and are release systemically from the small intestine. Since these enzymes act by hydrolysis amino acids located at the amino groups of terminal proteins inhibition of their processes would affect cell proliferation, secretion, invasion and angiogenesis. Small molecule inhibitors for the inhibition of aminopeptidases have been developed for oncological use. CHR-2797 is a pro-drug for an aminopeptidase inhibitor that is marketed by Chroma Therapeutics under the trade name of Tosedostat. Tosedostat aminopeptidase inhibitor under goes cellular modulation to the active metabolite (CHR79888) via hydrolysis of a methoxy group. This metabolite is poorly membrane permeable, resulting in cellular accumulation. In animal models Toseostad has proved to be a significant inhibitor of proliferation and has demonstrated anti-angiogenic activity. [Read the Full Post]

BORTEZOMIB – THE FIRST PROTEASOME INHIBITOR

2895 | Mar 19 2012

Introduction: Inhibition of the Proteasomes In the cellular environment there is a continuous movement of cells through cycles of life and death. Material is up taken and used to create new cells or energy, while protein signaling cascades regulate everything so that the host organism survives. However, during these essential processes proteins become damaged, unraveled or simply surplus to requirements, in this situation there exists clean up mechanisms to recycle as much material as possible. The major (>80%) pathway for this process is the proteasome pathway which in conjunction with the Ubiquitin pathway performs clean up routines in the cellular environment. The proteasome is a tubular protein sealed with another protein containing a tyrosine kinase domain. This tubular protein allows “tagged” protein to enter and bind within the tube section. Then catalytic activity begins to dismantle the protein and pass subunits out into the cytosole for reuse. Protein are recognized for destruction due to the actions of the Ubiquitin protein kinases. [Read the Full Post]

HDAC INHIBITOR AND ITS EEFICACY IN CANCER

3892 | Mar 19 2012

Introduction: Inhibition of Histone deacetylase function Checks and balances are key terms used when describing the modulation of the cell growth pathways and quality assurance mechanisms. Verification of every stage in the process is checked for completion and there should be a balance between cell growth & cell death depending on the circumstances. Balance is maintained via the signaling pathways, which require a chemical change to transmit their signals down the line. Typically, this is the phosphorylation of the tyrosine kinase-binding domain. This domain is found in the large super family of protein kinases that dominate the regulation of cell growth. However, phosphorylation is not the only mechanism of activation, acetylation can also be utilized and this is where the histone deacetylase proteins comes into play. HDAC´s have been classified into four categories of which class 1 HDAC´s are primarily located in the nucleus, and are linked to transcriptional activation. Class 2 HDAC´s carry signals from cytosole into the nucleus were transcriptional activities are triggered. Classes 3 and 4 are not well defined and have not been associated with cancer chemotherapy or any metabolic disorders to date. [Read the Full Post]

BELINOSTAT: THE UNUSUAL HDAC INHIBITOR

5218 | Mar 13 2012

Introduction: HDAC inhibition In humans, histone deacetylase (HDAC) is a regulatory enzyme located both in the cellular cytoplasm and in the nucleus. Its function is the removal of an acetyl group from both protein and non-protein targets, this removal is usually part of a signaling pathway inducing or reducing various activities within the cell. There are currently 18 isoforms of HDAC known which are classified into four classes. Class 1 are the nucleus HDAC´s (1,2,3&8); Class II HDAC´s (4, 5, 7 & 9) are located in either the cytoplasm, the nuclease or a transitional state between the two. These two classes of enzymes are related by the fact that they require a zinc catalyst for activity. Class III (6&10) and IV HDAC´s (11) do not require zinc for their activity but instead rely on NAD+ for their activity. [Read the Full Post]

RO4929097 – TARGETING NOTCH SIGNALING IN CANCER

6647 | Mar 13 2012

RO4929097: INHIBIT GAMMA SECRETASE: Gamma secretase is famous protease consists of several subunits complex. This enzyme is also recognized as inter-membrane protease as it cuts trans-membrane proteins. The most eminent gamma secretase example is breakage of amyloid precursor, a protein to produce amyloid beta peptide which is involved in the formation of amyloid plaques in patient’s brain who suffer with Alzheimer’s disease. In the present situation though, we concentrate on the key role of gamma secretase in the Notch protein processing. It has been found as there is link between anomalous notch signaling and many cancers. Hence the idea of targeting those enzymes which are responsible for the processing of Notch protein became the reason of RO4929097 gamma secretase inhibitor discovery. The inhibiting Notch signaling by using RO4929097 GS inhibitor has been confirmed by protein estimation methods like Biuret method etc. [Read the Full Post]

RO4929097 – CONTROLLING NOTCH SIGNALING IN TUMORS

6719 | Mar 13 2012

Introduction: Gamma secretase Inhibition Gamma secretase is an internal protease enzyme that is a complex of a number of subunits. Its mode of action is to cleave proteins that lie within the membrane-spanning domain, these include the amyloid precursor protein (APP) and the Notch. The Notch signaling pathway processes four different Notch receptors (1, 2, 3 and 4) which span the cell membrane. Upon extracellular interaction with a substrate protein the internal domain is released. This section of the protein then induced a signaling cascade within the cell nucleus to alter gene expression. The function of the various NOTCH proteins is varied but in terms of cancer notch receptors have been demonstrated to be down regulated in basal cells carcinomas and cervical cancers. Notch 1 over-expression is associated with acute T cell leukemia and breast cancer, Notch 3 receptor is over-expressed in 20% of ovarian cancers [5-7] while overexpression of Notch 4 is evident in murine models of breast cancer. The field of research into NOTCH signaling is vast and beyond the scope of this document, simple put there existed evidence that inhibition of aberrant NOTCH over-expression would be an ideal target for chemotherapeutic activity. The development of inhibitors which would affect the action of NOTCH led to the targeting of the Gamma secretase enzyme. Developed by Roche the RO4929097 gamma secretase inhibitor represents a potent novel small molecule that is orally bioavailable. [Read the Full Post]

HDACs, play important roles in kidney development

6256 | Sep 08 2011

Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and non-genomic effects. Some data suggest that HDACs may play a important role in kidney development. [Read the Full Post]

Yin, L., O. C. Velazquez, et al. (2010). "Notch signaling: emerging molecular targets for cancer therapy." Biochem Pharmacol 80(5): 690-701.

5715 | Jul 13 2011

This article is a review which give a presentation of Notch signal pathway and how the researchers target Notch signal pathway for a cancer therapy. [Read the Full Post]

Ekwall, K. (2005). "Genome-wide analysis of HDAC function." Trends Genet 21(11): 608-615.

3920 | Apr 19 2011

This review is about genome-wide analysis of HDAC functions. It is a review of systematic study of HDACs and introduces the related targets such as Rpd3, Hos1, Hos2 , Hos3 and so on. [Read the Full Post]

de Ruijter, A. J., A. H. van Gennip, et al. (2003). "Histone deacetylases (HDACs): characterization of the classical HDAC family." Biochem J 370(Pt 3): 737-749.

3988 | Mar 20 2011

This is an article which give us the detail of HDAC family member proteins. It introduce the members of HDAC family one by one. You can make different HDACs clear after reading this article. [Read the Full Post]