Epigenetics

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

2 | May 06 2021

Shuiyan Wu et al. thought that the BRD4 degrader ARV-825 could effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

1 | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment

2 | Apr 30 2021

Sophia Thy et al. thought that BETi could be used to "episensitize" UC cells to cytotoxic chemotherapy and inhibitors of DNA repair by inducing BRCAness in non BRCA1/2 mutated cancers. [Read the Full Post]

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib

1 | Apr 29 2021

Xiao-Ru Zhou et al. provided a promising combination therapy for MCL and highlighted the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor. [Read the Full Post]

MLL1 combined with GSK3 and MAP2K inhibition improves the development of in vitro-fertilized embryos

1 | Apr 27 2021

Xuejie Han et al. found that the application of 3i provided a new method for improving IVF embryo production in domestic animals. [Read the Full Post]

H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

4 | Apr 25 2021

Jessica Connacher et al. found that H3K36me2&3-associated repression of genes was therefore involved in key transcriptional shifts that accompanied the transition from early gametocyte differentiation to intermediate development. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

5 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

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

3 | Apr 15 2021

Jung Yoo et al. found synergy between paclitaxel and HDAC6-selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6-selective inhibitors, not only in ovarian cancer but also in other tumors. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

3 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat

3 | 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

3 | Apr 13 2021

Golebagh Rahmani et al. highlighted the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy. [Read the Full Post]

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

4 | Apr 11 2021

Juan Bayo et al. found that mutations and changes in expression of epigenetic modifiers were common events in human hepatocellular carcinoma, leading to an aggressive gene expression program and poor clinical prognosis. [Read the Full Post]

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function

4 | Apr 10 2021

Adam P Cribbs et al. found that compelling argument for further clinical investigation. [Read the Full Post]

Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

4 | Apr 07 2021

Mu-Chen Zhang et al. found that CR-CHOP was effective and safe in elderly patients with newly diagnosed DLBCL. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

4 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

3 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells

5 | Mar 30 2021

Xueyuan Cheng et al. found that the combination treatment inhibits cell viability, formation of colonies, increased apoptosis and cell cycle arrest at G0-G1. [Read the Full Post]

Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy

9 | Mar 24 2021

Zhonghai Shen et al. thought that HDAC6 inhibition prevented OA development, and HDAC6 could be applied as a potential therapeutic target for OA management. [Read the Full Post]

Oxidative stress abrogates the degradation of KMT2D to promote degeneration in nucleus pulposus

6 | Mar 23 2021

Wenbin Xu et al. approved that oxidative stress induced ROS production promote the process of NP degeneration by enhancing KMT2D mediated transcriptional regulation of matrix degeneration related genes during NP degeneration. [Read the Full Post]

Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity

7 | Mar 21 2021

Kongkai Zhu et al. described the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. [Read the Full Post]

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

7 | Mar 19 2021

Seiichi Okabe et al. suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors. [Read the Full Post]

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

7 | Mar 12 2021

Sailu Sarvagalla et al. found that a possible means to develop sub-type selective inhibitor was by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. [Read the Full Post]

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

7 | Mar 12 2021

Nina Schmid et al. found that several SIRTs were expressed by GCTs, and SIRT1 and SIRT3 were involved in the growth regulation of KGN. [Read the Full Post]

A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival

7 | Mar 11 2021

Yvonne de Jong et al. thought that AURKA, CHK1 and PLK1 were identified as important survival genes in chondrosarcoma cell lines. [Read the Full Post]

Sublethal irradiation promotes the metastatic potential of hepatocellular carcinoma cells

7 | Mar 08 2021

Yulin Cao et al. indicated that MMP-8 secreted by irradiated NPCs enhanced the migration and invasion of HCC by regulating AMPK/mTOR signaling, revealing a novel mechanism mediating sublethal irradiation-induced HCC metastasis at the level of the tumor microenvironment. [Read the Full Post]

Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

10 | Mar 05 2021

Yoshifumi Tada et al. found that baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. [Read the Full Post]

In-vitro evaluation of the immunomodulatory effects of baricitinib: implication for COVID-19 therapy

7 | Mar 04 2021

Linda Petrone et al. found that exogenous addition of baricitinib decreased the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. [Read the Full Post]

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

9 | Mar 02 2021

Xiaowen Bi et al. suggested that CBP bromodomain could serve as a candidate therapeutic target for the treatment of lethal sepsis via inhibiting LPS-induced expression and release of HMGB1 and suppressing the pro-inflammatory activity of HMGB1. [Read the Full Post]

Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

9 | Feb 16 2021

Lotta Pohjolainen et al. showed similar hypertrophic responses to PKC modulators in NRVMs and hiPSC-CMs. [Read the Full Post]

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

29 | Feb 07 2021

Qiang Liu et al. suggested that SLP-2 controlled the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

23 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer

15 | Jan 31 2021

Ziyi Sun et al. found that PIM1 was a poor prognostic factor for NSCLC. [Read the Full Post]

Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis

17 | Jan 30 2021

Thomas M Hofbaue et al. found mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components. [Read the Full Post]

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

18 | Jan 29 2021

Xing Liu et al. found that EPZ015666 inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. [Read the Full Post]

Inhibition of PRMT5 Attenuates Oxidative Stress-Induced Pyroptosis via Activation of the Nrf2/HO-1 Signal Pathway in a Mouse Model of Renal Ischemia-Reperfusion Injury

20 | Jan 29 2021

Changhui Diao et al. thought that PRMT5 might be a promising therapeutic target. [Read the Full Post]

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

14 | Jan 22 2021

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

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules

15 | Jan 22 2021

Ji-Sheng Wang et al. found that "leech-centipede" medicine could improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protected endothelial function and anti-platelet activation. [Read the Full Post]

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer

18 | Jan 17 2021

R Vatapalli et al. thought that DOT1L selectively regulated the tumorigenicity of AR-positive prostate cancer cells and was a promising therapeutic target for PCa. [Read the Full Post]

Targeting LSD1 for acute myeloid leukemia (AML) treatment

23 | Jan 14 2021

Shujing Zhang et al. discussed the main epigenetic drugs targeting LSD1 for AML therapy. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

17 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

18 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [Read the Full Post]

Effects and Mechanism of Action of PX-478 in Oxygen-Induced Retinopathy in Mice

19 | Jan 07 2021

Xiaoyan Pan et al. found that HIF-1α played a main role in OIR and could be considered a therapeutic target in OIR by suppressing downstream angiogenic factors, PX-478 decreasing the retinal avascular area and NV. [Read the Full Post]

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

19 | Jan 01 2021

Ahlam Ali et al. found that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC. [Read the Full Post]

Pan- and Isoform-specific Inhibition of the Bromodomain and Extra-terminal Proteins and Evaluation of Synergistic Potential With Entospletinib in Canine Lymphoma

16 | Dec 27 2020

Weibo Kong et al. showed that Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET. [Read the Full Post]

Small molecular compounds efficiently convert human fibroblasts directly into neurons

0 | Dec 26 2020

Jijuan Yang et al. found that a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons. [Read the Full Post]

Targeted therapy of TERT-rearranged neuroblastoma with BET bromodomain inhibitor and proteasome inhibitor combination therapy

21 | Dec 24 2020

Jingwei Chen et al. showed that OTX015 and carfilzomib combination therapy was likely to be translated into the first clinical trial of a targeted therapy in TERT-rearranged neuroblastoma patients. [Read the Full Post]

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells

22 | Dec 22 2020

Xuejian Zhou et al. indicated that Artesunate induced autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells. [Read the Full Post]

AMPK mediates energetic stress-induced liver GDF15

24 | Dec 21 2020

Logan K Townsend et al. proved that AMPK played a role in mediating the induction of GDF15 under conditions of energetic stress in mouse liver in vivo. [Read the Full Post]

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

28 | 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

22 | 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

22 | 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

23 | 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

22 | 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

24 | Dec 12 2020

Hanna Jung et al. indicated that MGCD, an HDAC inhibitor, attenuated aortic remodeling in rats with TAC-induced pressure overload rats and might serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases. [Read the Full Post]

Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of MLL-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML

23 | Dec 09 2020

Annalisa Lonetti et al. highlighted a novel therapeutic strategy for pediatric AML patients. [Read the Full Post]

HDAC6-selective inhibitors decrease nerve-injury and inflammation-associated mechanical hypersensitivity in mice

26 | Dec 02 2020

Farhana Sakloth et al. suggested that inhibition of HDAC6 provided a promising therapeutic avenue for the alleviation of mechanical allodynia associated with peripheral nerve injury and peripheral inflammation. [Read the Full Post]

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

27 | Nov 22 2020

Sabina Luszczak et al. believed that a co-targeting approach was a viable therapeutic strategy that should be developed further in pre-clinical studies. [Read the Full Post]

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

30 | Nov 18 2020

Isabella J Brouwer et al. suggested that STAT3 played a preferential role in the mechanism of action of these cucurbitacins. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Nov 14 2020

Laurie K Svoboda et al. demonstrated that the SSP was highly active in Ewing sarcoma and that its oncogenic activation was maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Activating JAK-mutations confer resistance to FLT3 kinase inhibitors in FLT3-ITD positive AML in vitro and in vivo

29 | Nov 10 2020

Christoph Rummelt et al. characterized a novel mechanism of resistance to FLT3-ITD inhibition and might offer a potential therapy, using dual JAK and FLT3 inhibition. [Read the Full Post]

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGFß and EGFR signaling pathways in obstructive nephropathy

36 | Oct 28 2020

Xingying Chen et al. indicated that HDAC6 inhibition could attenuate development of renal fibrosis by suppression of TGFb1 and EGFR signaling, and suggested that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis. [Read the Full Post]

Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways

38 | Oct 26 2020

Guangfeng Long et al.found that the protective effect of FG-4592 on DOX-induced cardiotoxicity possibly through upregulating HIF-1α and its target genes antagonizing apoptosis and oxidative stress. [Read the Full Post]

Piceatannol reduces resistance to statins in hypercholesterolemia by reducing PCSK9 expression through p300 acetyltransferase inhibition

35 | Oct 25 2020

Hyo-Jin Kim et al. indicated that PT was a new nutraceutical candidate to reduce the statin resistance and tolerance that occured in patients with hypercholesterolemia. [Read the Full Post]

Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis

33 | 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

37 | 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

35 | Oct 14 2020

Carolina Martinelli et al.documented the possibility to easily generate scalable nanovesicles with specific therapeutic cargo modifications useful in different drug delivery contexts. [Read the Full Post]

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

43 | Oct 02 2020

Nicholas D LeBlond et al. suggested that intervention with the first-generation AMPK activator A-769662 was not able to stem the progression of atherosclerosis. [Read the Full Post]

Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors

35 | Sep 29 2020

Qifei Li et al. supported that this novel compound 13f provided a perspective for developing effective BRD4 inhibitors. [Read the Full Post]

CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR

37 | Sep 24 2020

Adhikarimayum Lakhikumar Sharma et al. demonstrated that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. [Read the Full Post]

AGE-Induced Suppression of EZH2 Mediates Injury of Podocytes by Reducing H3K27me3

42 | Sep 23 2020

Marita Liebisch et al. provided a novel pathway how AGEs contributed to podocyte injury and the formation of the so-called metabolic memory in DKD. [Read the Full Post]

Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia

51 | Sep 22 2020

Yitao Huang et al. presented a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions. [Read the Full Post]

Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis

43 | Sep 21 2020

Rajesh K Kasam et al. provided important proof-of-concept that demonstrated barasertib as a possible intervention therapy for IPF. [Read the Full Post]

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets

39 | Sep 21 2020

Julia Krushkal et al. indicated potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggested targets for combination therapies. [Read the Full Post]

Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes

42 | Sep 16 2020

Yingjie Wang et al. suggested the Mst1-AMPK-Sirt1 axis was a potential target for RA therapy. [Read the Full Post]

SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway

46 | Sep 16 2020

Yangyang Li et al. proposed that the discovery of the effect of SIRT1 on neuropathic pain in the VTA represented an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway. [Read the Full Post]

Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells

72 | Sep 10 2020

Kazuki Okubo et al. found that there was a positive feedback cycle among AMPK activation, histone acetylation, and ER stress induction. [Read the Full Post]

Sotrastaurin, a PKC inhibitor, attenuates RANKL-induced bone resorption and attenuates osteochondral pathologies associated with the development of OA

44 | Sep 08 2020

Cong Pang et al. provided evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. [Read the Full Post]

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing

54 | Aug 31 2020

Frank M Davis et al. concluded that palmitate contributed to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy might represent a novel treatment for nonhealing diabetic wounds. [Read the Full Post]

Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells

62 | Aug 30 2020

Maria Wiese et al. found that combinatorial treatment with CBP and BET inhibitors was highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy. [Read the Full Post]

Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic β-cells

58 | Aug 30 2020

Ye-Jee Lee et al. suggested that SIRT1 was a potential target for the protection of pancreatic β-cells against hypoxic damage during ITx. [Read the Full Post]

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

66 | Aug 28 2020

Zhaodong Wang et al.showed that EpSCs were used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering.Quercetin was a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

126 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

The Antitumor Efficiency of Zinc Finger Nuclease combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

67 | 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

71 | Aug 13 2020

Shu-Nan Cui et al. showed that TSA promoted the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improved the survival of mice with polymicrobial sepsis. [Read the Full Post]

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

93 | Aug 10 2020

Jingyu Deng et al. showed that Irisin played a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. [Read the Full Post]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes

89 | Aug 10 2020

Adrien Foca et al. emphasized that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies. [Read the Full Post]

EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets

65 | Aug 08 2020

Juraj Adamik et al. found that EZH2 exhibits complex roles in supporting osteoclast differentiation and function. [Read the Full Post]

Pentraxin-3 Mediates Prosurvival Actions of Interferon Tau in Bovine Luteinized Granulosa Cells

91 | Aug 06 2020

Raghavendra Basavaraja et al. suggested a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage. [Read the Full Post]

PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity

91 | Aug 03 2020

Hyungsoo Kim et al. provided a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response. [Read the Full Post]

In Vitro and In Vivo Efficacy of DNA Damage Repair Inhibitor Veliparib in Combination with Artesunate against Echinococcus granulosus

96 | Aug 02 2020

Y F Li et al. demonstrated that AS or AS in combination with Veliparib was effective for treating CE, especially the combination group. [Read the Full Post]

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer

101 | Aug 02 2020

Yifan Jiang et al. found that PARP inhibitors were an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer. [Read the Full Post]

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data

168 | Jul 28 2020

Mahdi Gharaibeh et al. showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. [Read the Full Post]

4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism

117 | Jul 18 2020

Weili Wang et al. provided a novel therapeutic strategy for MDS. [Read the Full Post]

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial

121 | Jul 17 2020

Andrew M Brunner et al. suggested that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. [Read the Full Post]

Protein Acetylation Derepresses Serotonin Synthesis to Potentiate Pancreatic Beta-Cell Function Through HDAC1-PKA-Tph1 Signaling

155 | 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)

171 | 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

183 | 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

163 | 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

152 | 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

158 | Jul 01 2020

Zude Chen et al. provided not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. [Read the Full Post]

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia

113 | Jun 28 2020

Mursal Sherzai et al. showed that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. [Read the Full Post]

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid

110 | Jun 24 2020

Mariah M Hoffman et al. indicated that 4SC-202 had both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and was an important potential cancer therapeutic to be investigated in vivo. [Read the Full Post]

EZH2 Is Involved in Vulnerability to Neuroinflammation and Depression-Like Behaviors Induced by Chronic Stress in Different Aged Mice

106 | Jun 23 2020

Wei Wang et al. found that EZH2 might be involved in susceptibility to neuroinflammation and depression-like behaviors in different aged mice. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

206 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

127 | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

213 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

Revealing the Selective Mechanisms of Inhibitors to PARP-1 and PARP-2 via Multiple Computational Methods

132 | Jun 17 2020

Hongye Hu et al. provided new insights about how inhibitors specifically bound to PARP-1 over PARP-2, which might help facilitate the design of highly selective PARP-1 inhibitors in the future. [Read the Full Post]

Mechanism and Current Progress of Poly ADP-ribose Polymerase (PARP) Inhibitors in the Treatment of Ovarian Cancer

0 | Jun 15 2020

Feiyue Zheng et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

205 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

Cell Cycle Arrest and Apoptosis Are Not Dependent on p53 Prior to p53-dependent Embryonic Stem Cell Differentiation

257 | Jun 02 2020

Sushil K Jaiswal et al. found that the multiple roles of p53 in cell cycle regulation and apoptosis were first acquired during pluripotent stem cell differentiation. [Read the Full Post]

CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors

113 | Jun 01 2020

Emmanuel S Antonarakis et al. found that CDK12-altered prostate cancer was an aggressive subtype with poor outcomes to hormonal and taxane therapies as well as to PARP inhibitors. A proportion of these patients might respond favorably to PD-1 inhibitors, which implicated CDK12 deficiency in immunotherapy sensitivity. [Read the Full Post]

Small Molecule JQ1 Promotes Prostate Cancer Invasion via BET-independent Inactivation of FOXA1

150 | May 31 2020

Leiming Wang et al. indicated that JQ1 has an unexpected effect of promoting invasion in prostate cancer. [Read the Full Post]

PARP and PARG Inhibitors in Cancer Treatment

122 | May 28 2020

Dea Slade highlighted clinical performance of four PARP inhibitors used in cancer therapy (olaparib, rucaparib, niraparib, and talazoparib) and discussed the predictive biomarkers of inhibitor sensitivity, mechanisms of resistance as well as the means of overcoming them through combination therapy. [Read the Full Post]

Talazoparib in Patients With a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses From the Phase III EMBRACA Trial

128 | May 27 2020

Sara A Hurvitz et al. found that Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

199 | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase 2 study.

129 | May 15 2020

Lampert EJ et al. found that he PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Their correlative study results suggested immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination [Read the Full Post]

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay

131 | May 13 2020

Sirisena N et al. highlighted the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants. [Read the Full Post]

Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha

135 | May 10 2020

Koh MY et al. concluded that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors. [Read the Full Post]

Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination With Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma

172 | Apr 27 2020

Dan T Vogl et al. showed that at the recommended phase II dose of ricolinostat of 160 mg daily, the combination with bortezomib and dexamethasone is safe, well-tolerated, and active, suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy. [Read the Full Post]

The BET Bromodomain Inhibitor i-BET151 Impairs Ovarian Cancer Metastasis and Improves Antitumor Immunity

125 | Apr 15 2020

Ai Liu et al. showed that tumor metastasis may be suppressed by i-BET151 via the Stat3 pathway; this approach could be used as a strategy for the treatment of OC. [Read the Full Post]

Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC

139 | Apr 15 2020

Jonathan Welti et al. showed that BETi merit clinical evaluation as inhibitors of AR splicing and function, with trials demonstrating their blockade in proof-of-mechanism pharmacodynamic studies. [Read the Full Post]

OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models

118 | Apr 13 2020

Berenguer-Daizé C et al. demonstrated with OTX015 tumor levels 7 to 15-fold higher than in normal tissues, along with preferential binding of OTX015 to tumor tissue. The significant antitumor effects seen with OTX015 in GBM xenograft models highlight its therapeutic potential in GBM patients, alone or combined with conventional chemotherapies. [Read the Full Post]

Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance

214 | Apr 09 2020

Jane EP et al. provided new insights into mechanisms of treatment resistance in gliomas, hold promise for targeting recurrent disease, and provided a potential strategy for further exploration of next generation inhibitors. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

165 | Mar 30 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Bcl-2high mantle cell lymphoma cells are sensitized to acadesine with ABT-199

129 | Mar 23 2020

Montraveta A et al. supported the notions that antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and that the combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. [Read the Full Post]

Biguanides Induce Acute de novo Lipogenesis in Human Primary Sebocytes

124 | Mar 22 2020

Nicoll J et al. found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response. Biguanides did not activate AMPK in sebocytes, however, they significantly reduced oxygen consumption rate and increased lactate production. Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes. [Read the Full Post]

JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis

225 | 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

201 | 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

210 | 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

213 | 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

360 | Mar 08 2020

Huang HJ et al. revealed MGCD0103 could be a potential therapeutic agent against AD. [Read the Full Post]

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

197 | Mar 06 2020

Briere D et al. provided evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy. [Read the Full Post]

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

187 | Mar 03 2020

Marcos-Villar Let al. supported a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

171 | Feb 17 2020

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

290 | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

164 | Feb 11 2020

Sun C found that MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. [Read the Full Post]

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

169 | Feb 10 2020

Wang H found that PARP trapping combined with specific pro-oxidative agents may provide safe and effective ways to broaden the therapeutic potential of PARP inhibitors. [Read the Full Post]

The histone deacetylase inhibitor romidepsin spares normal tissues while acting as an effective radiosensitiser in bladder tumours in vivo

207 | 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

206 | Feb 07 2020

Zhang AL et al. provided new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway

192 | Jan 31 2020

Zhang H et al. demonstrated that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provided preclinical proof-of-principle evidence for targeting EZH2 in patients with MB. [Read the Full Post]

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

191 | Jan 25 2020

Tremblay G et al. indicated that MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment. [Read the Full Post]

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells

178 | Jan 21 2020

Liu C et al. indicated that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation. [Read the Full Post]

Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer

294 | Jan 21 2020

Zheng F et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations

190 | Jan 20 2020

Jerez Y et al. discussed the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling. [Read the Full Post]

Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status

166 | Jan 20 2020

Venneker S et al. suggested that talazoparib combined with temozolomide or radiation are promising therapeutic strategies for chondrosarcoma, irrespective of IDH mutation status. A subset of chondrosarcomas may be deficient in nonclassical DNA repair pathways, suggesting that PARP inhibitor sensitivity is multifactorial in chondrosarcoma. [Read the Full Post]

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

223 | Jan 03 2020

Cao J et al. showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC. [Read the Full Post]

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

0 | Jan 01 2020

Wang YM et al. suggested that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment. [Read the Full Post]

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

182 | Jan 01 2020

Yang Y et al. indicated that FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI. [Read the Full Post]

Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

315 | Dec 31 2019

Chen X et al. suggested the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

0 | Dec 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia

219 | 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

213 | 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

216 | Dec 16 2019

Bettica P et al. showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years. [Read the Full Post]

Reactive oxygen species generation and increase in mitochondrial copy number: new insight into the potential mechanism of cytotoxicity induced by aurora kinase inhibitor, AZD1152-HQPA

217 | Dec 13 2019

Zekri A et al. showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA. [Read the Full Post]

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

234 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

0 | Dec 08 2019

Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death

156 | Dec 01 2019

Tam EK et al. identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

0 | Dec 01 2019

Miranda TB et al. found that upon removal of DZNep, gene expression is reduced to its original state. This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

422 | Nov 29 2019

Evanno E et al. showed that histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

0 | Nov 28 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Salidroside attenuates dextran sulfate sodium-induced colitis in mice via SIRT1/FoxOs signaling pathway

228 | Nov 22 2019

Li H et al. manifested that Sal may protect colitis mice by activating the SIRT1/FoxOs pathway, which is related to oxidative stress and apoptosis in colon tissues. [Read the Full Post]

Combinational therapeutic targeting of BRD4 and CDK7 synergistically induces anticancer effects in head and neck squamous cell carcinoma

144 | Nov 21 2019

Zhang W et al. revealed a novel therapeutic strategy of pharmacological inhibitions of BRD4 and CDK7 against HNSCC. [Read the Full Post]

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

226 | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

0 | Nov 11 2019

Ren Y et al. showed the Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

244 | 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

282 | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels

163 | Oct 19 2019

Li N et al. indicated that dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer. [Read the Full Post]

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

251 | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts

238 | Oct 14 2019

Yuan AL et al. indicated that in laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ. [Read the Full Post]

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

233 | Oct 13 2019

Coleman RL et al. indicated that across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. [Read the Full Post]

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer

279 | Oct 11 2019

Noblejas-López MDM et al. provided options for further clinical development of these agents in TNBC. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

320 | Oct 11 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

398 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways

340 | Oct 05 2019

Wu Y et al. suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed. [Read the Full Post]

Entinostat for the treatment of breast cancer

294 | 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

312 | 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

676 | 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

332 | 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

315 | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

271 | Sep 08 2019

Yamamoto TM et al. demonstrated that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors. [Read the Full Post]

Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

263 | Sep 08 2019

Dockery LE et al. indicated this article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib's companion diagnostic test. [Read the Full Post]

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

374 | 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

349 | 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

338 | Sep 02 2019

Shi B et al. showed that overexpression of EZH2 is a negative prognostic indicator. Increased EZH2 expression predicts for response to HDAC inhibitors and thus could serve as a biomarker for selecting NSCLC patients for treatment with HDAC inhibitors. [Read the Full Post]

PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer

224 | Aug 30 2019

Liu B et al. demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models. [Read the Full Post]

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

0 | Aug 27 2019

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126in patients with MM may be warranted. [Read the Full Post]

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

684 | Aug 25 2019

He Y et al. revealed that ΔNp63 mediated anticancer effects of metformin and 4SC-202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC-202 treatment. Collectively, metformin and 4SC-202 synergistically promote intrinsic apoptosis through accelerating ubiquitin-mediated degradation of ΔNp63 in OSCC, and this co-treatment can serve as a potential therapeutic scheme for OSCC. [Read the Full Post]

Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma

260 | Aug 20 2019

Kurokawa C et al. showed that alisertibdisplays significant antitumor activity against primary GBM lines and xenografts, including patient derived GBM lines resistant to bevacizumab; these data support clinical translation in GBM. [Read the Full Post]

Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

284 | Aug 20 2019

Levesley J et al. indicated that selective small-molecule inhibitors of BCL-XL may enhance the efficacy of MLN8237 and other targeted chemotherapeutic agents. [Read the Full Post]

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma

263 | Aug 19 2019

Knutson SK et al. indicated these data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. [Read the Full Post]

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

312 | Aug 18 2019

Disney AJ et al. reported that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. [Read the Full Post]

PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation

329 | Aug 17 2019

Michmerhuizen AR et al. demonstrated that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT +/- PARPi in women with IBC [Read the Full Post]

Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review.

241 | Aug 17 2019

Boussios S et al. discussed multiple clinical trials that are underway examining the antitumor activity of such combination strategies. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

487 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Targeting autophagy potentiates the anti-tumor effect of PARP inhibitor in pediatric chronic myeloid leukemia

260 | Aug 07 2019

Liu Y et al. demonstrated that autophagy played a cyto-protective role in talazoparib-treated pediatric CML and co-treatment with talazoparib and autophagy inhibitor could induce synergetic anti-tumor effect, providing novel insights for pediatric CML treatment. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

0 | Jul 27 2019

JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma

184 | Jul 25 2019

Garcia PL et al. suggested that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. [Read the Full Post]

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

247 | Jul 22 2019

Belz JE et al. demonstrated that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. [Read the Full Post]

The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells

223 | Jul 14 2019

Arun B et al. indicated that the patients with BRCA1 allelic loss may also benefit from PARP inhibitor therapy if BRCA is further inhibited. [Read the Full Post]

BRCA1, PARP1 and γH2AX in acute myeloid leukemia: Role as biomarkers of response to the PARP inhibitor olaparib

615 | Jul 14 2019

Faraoni I et al. showed the high sensitivity of AML blasts and the identification of biomarkers potentially able to predict response and/or resistance may foster further investigation of olaparib monotherapy for AML patients unfit to conventional chemotherapy. [Read the Full Post]

A patent review of arginine methyltransferase inhibitors (2010-2018)

290 | Jul 10 2019

Li X et al. summarized the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

464 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers

291 | Jul 03 2019

Katoh M indicated that SMO inhibitors can remodel the immunosuppressive TME that is dominated by M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells and regulatory T cells, and thus, a Phase I/II clinical trial of the immune checkpoint inhibitor pembrolizumab with or without vismodegib in BCC patients is ongoing. [Read the Full Post]

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells

265 | Jun 26 2019

Cao YP et al. demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested. [Read the Full Post]

Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells

417 | 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

284 | 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

305 | 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

889 | Jun 19 2019

Zhang WB et al. showed that ACY-1215 has potential therapeutic value in mice with ALF by directly inhibiting inflammatory response via regulation of the TLR4-MAPK/NF-kB pathway. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

367 | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

310 | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

321 | May 27 2019

Zekri A et al. showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. [Read the Full Post]

Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive acute myeloid leukemia

388 | May 25 2019

Luskin MR et al. indicated that expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

414 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition

283 | May 19 2019

Gabbasov R et al. suggested that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents. [Read the Full Post]

Hydroxysafflor yellow A inhibited lipopolysaccharide-induced non-small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

216 | May 18 2019

HYSA suppressed LPS-mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation-mediated NSCLC. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

404 | May 09 2019

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

370 | May 07 2019

Thromboembolic events in polycythemia vera

616 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

669 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

1154 | Apr 21 2019

Lim RR et al. concludd that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. [Read the Full Post]

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer

406 | Apr 14 2019

Kirschner AN et al. showed that PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation. [Read the Full Post]

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

449 | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

290 | Apr 09 2019

Moore KN et al. identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. [Read the Full Post]

Roxadustat in the treatment of anaemia in chronic kidney disease

398 | Mar 31 2019

Del Vecchio L et al showed that Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies. [Read the Full Post]

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China

383 | Mar 31 2019

Chen N et al. showed that FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program. [Read the Full Post]

MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer

334 | Mar 29 2019

Yi J et al. show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

419 | Mar 28 2019

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

378 | Mar 28 2019

Lux S et al. showed that acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

395 | Mar 24 2019

Ren Y et al. indicated that the Sirt1 activator, SRT1720, exerts protective effects against UUO-induced tubulointerstitial fibrosis. The mechanisms of action of SRT1720 may include, at least in part, the suppression of renal oxidative stress and the TGF-β1/CTGF signalling pathway. The Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury

428 | Mar 12 2019

Schmitt HM et al. showed the inhibition of HDAC3 activity with systemic dosing of RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss after acute optic nerve injury. [Read the Full Post]

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

258 | Mar 11 2019

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

490 | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway

232 | Mar 08 2019

Zhao X et al. demonstrated that compound C inhibited the phosphorylation of JNK and its target c-Jun. Blocking JNK by SP600125 or siRNA suppressed autophagy induction upon compound C treatment. Moreover, compound C induced p38 MAPK activation, and its inhibition promoted autophagy induction via JNK activation. In addition, compound C induced p53 expression, and its inhibition attenuated compound C-induced autophagic response. Thus, compound C triggers autophagy, at least in part, via the JNK and p53 pathways in human CCA cells. In conclusion, suppresses autophagy could increase compound C sensitivity in human CCA. [Read the Full Post]

In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors

231 | Mar 07 2019

Hao J et al. demonstrated the potential of zebrafish as an attractive complementary platform for drug development that incorporates an assessment of in vivo bioactivity and selectivity in the context of a living organism. [Read the Full Post]

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

400 | Mar 06 2019

Bao B et al. indicated that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. [Read the Full Post]

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients

409 | Mar 03 2019

Tedesco-Silva H et al. indicated that sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

411 | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes

256 | Feb 26 2019

Aury-Landas J et al. showed DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

291 | Feb 26 2019

Miranda TB et al. suggested that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

342 | Feb 18 2019

PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia

243 | Feb 08 2019

Guo H et al. found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia. [Read the Full Post]

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

441 | Feb 07 2019

Martin MJ et al. supported a model in which the combination of osimertinib and OxPhos inhibitors can delay or prevent resistance in osimertinib-naïve tumour cells, and represents a novel strategy that warrants further pre-clinical investigation. [Read the Full Post]

Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism

1313 | 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

531 | Jan 09 2019

Yang X et al. demonstrated that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

0 | Jan 07 2019

Valdez BC et al. further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity

1043 | Jan 03 2019

Borriello F et al. provided insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity. [Read the Full Post]

Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

453 | Jan 02 2019

Bernasconi E et al. indicated the use of combination schemes targeting EZH2, mTOR and BTK alongside BET bromodomains. [Read the Full Post]

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

469 | Jan 02 2019

Parasramka M et al. showed that NEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies. [Read the Full Post]

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification

445 | Dec 31 2018

Gherardi S et al. suggested therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

838 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Enhanced efficacy of 5-fluorouracil in combination with a dual histone deacetylase and phosphatidylinositide 3-kinase inhibitor (CUDC-907) in colorectal cancer cells

685 | 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

718 | Dec 26 2018

Ali D et al. revealed that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation. [Read the Full Post]

Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

274 | Dec 25 2018

Eyer L et al. indicated that high antiviral activity and low cytotoxicity of C2' methylated or C4' azido substituted pharmacophores suggest that such compounds might represent promising candidates for further development of potential therapeutic agents in treating TBEV infection. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

568 | Dec 20 2018

Valdez BC et al. further implied the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

465 | Dec 15 2018

Chhajer R et al. identified an Aurora kinase homolog in L. donovani implicated in cell-cycle progression, whose inhibition led to aberrant changes in cell-cycle progression and reduced viability. [Read the Full Post]

Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute lymphoblastic leukemia

519 | Dec 13 2018

Spartà AM et al. indicated that PLK1 and AK inhibitors display the potential for being employed in innovative therapeutic strategies for improving T-ALL patient outcome. [Read the Full Post]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

870 | Dec 09 2018

Zhang M et al. indicated that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system. [Read the Full Post]

Regulatory Mechanisms Underlying the Expression of Prolactin Receptor in Chicken Granulosa Cells

327 | Dec 08 2018

Hu S et al. provided new insights into the regulatory mechanisms controlling the expression of PRLR in granulosa cells. [Read the Full Post]

PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage

1152 | Dec 05 2018

Chen T et al. indicated that PARP inhibition through PJ34 might be an important therapeutic drug for SAH. [Read the Full Post]

AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells

389 | Dec 04 2018

Zhang TG et al. showed that AMPK activator acadesine (AICAR) alleviated INH-caused impairment of mitochondrial biogenesis by activation of silent information regulator two ortholog 1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC1 α) pathway in HepG2 cells. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

826 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

3499 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

0 | Nov 20 2018

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo

1160 | Nov 19 2018

Zhu Y et al. indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC. [Read the Full Post]

Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued transcription of HIF-1α in human umbilical vein endothelial cells

1151 | Nov 19 2018

Zhu J et al. suggested that oxytocin receptor signaling promoted the angiogenic behaviors of HUVECs via Gli1-indcued transcription of HIF-1α. We provided novel molecular insights into endothelial cell-mediated angiogenesis. [Read the Full Post]

Epigenetic drug combination induces remission in mouse xenograft models of pediatric acute myeloid leukemia

560 | Nov 18 2018

Gopalakrishnapillai A et al. indicated the expression of mutant p53 in MV4;11 cells reduced sensitivity to azacitidine-panobinostat combination, suggesting that p53 may be a predictor of response to epigenetic therapy in pediatric AML. [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

781 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

959 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Effects of the histone deacetylase inhibitor 'Scriptaid' on the developmental competence of mouse embryos generated through round spermatid injection

625 | 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

1031 | Nov 08 2018

Revalde JL et al. concluded that curcumin and A13 are inhibitors of the ENT1 transporter, but only at high concentrations (2-20µM). [Read the Full Post]

Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

597 | Nov 03 2018

Yuan J et al. suggested that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1020 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

580 | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

589 | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4

389 | Oct 06 2018

Castex J et al. showed that by repression of Sirt4, Lsd1 directs the epigenetic control of TSC immortality via maintenance of metabolic flexibility. [Read the Full Post]

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

0 | Oct 04 2018

Grandy RA et al. established a new dimension of chromatin regulation important in the maintenance of pluripotency. [Read the Full Post]

CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency

734 | Sep 18 2018

Wang XQ et al. demonstrated an essential role for the CDK1-PDK1-PI3K/Akt kinase signaling pathway in the regulation of self-renewal, differentiation, and somatic reprogramming, which provides a novel kinase cascade mechanism for pluripotency control and acquisition. [Read the Full Post]

P-TEFb Kinase Activity Is Essential for Global Transcription, Resumption of Meiosis and Embryonic Genome Activation in Pig

670 | Sep 18 2018

Oqani RK et al. suggested that P-TEFb kinase activity is crucial for oocyte maturation, embryo development and regulation of RNA transcription in pig. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

947 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Sep 03 2018

Pu Y et al. suggested that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

1159 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human

602 | Aug 18 2018

Jia L et al. illustrated a potential translational research bridging animal models and human studies. [Read the Full Post]

Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage

0 | Aug 08 2018

Vienken H et al. showed that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

0 | Aug 08 2018

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

873 | Aug 05 2018

Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

741 | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

1124 | 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

821 | 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

2447 | 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

805 | Jul 31 2018

Ni L et al. showed that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. [Read the Full Post]

GSK621 Targets Glioma Cells via Activating AMP-Activated Protein Kinase Signalings

491 | Jul 26 2018

Jiang H et al. summarized that GSK621 inhibits human glioma cells possibly via activating AMPK signaling. This novel AMPK activator could be a novel and promising anti-glioma cell agent. [Read the Full Post]

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

689 | Jul 25 2018

Yang T et al. indicated that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. [Read the Full Post]

Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

613 | Jul 24 2018

Wang GF et al. identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases. [Read the Full Post]

Downregulation of the PHLDA1 gene in IMR-32 neuroblastoma cells increases levels of Aurora A, TRKB and affects proteins involved in apoptosis and autophagy pathways

616 | Jul 24 2018

Durbas M et al. showed possible links of the protein to regulation of features of mitochondria and formation of autophagosomes. [Read the Full Post]

The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia

823 | 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

771 | Jul 22 2018

Dai Y et al. identified clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jul 20 2018

Laporte AN, et al. indicated this assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

1196 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway

1903 | Jul 04 2018

Deng H, et al. indicated RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

2687 | Jul 03 2018

Gu S et al. demonstrated that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Jul 03 2018

Meng Z, et al. indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Small molecule epigenetic screen identifies novel EZH2 and HDAC inhibitors that target glioblastoma brain tumor-initiating cells

474 | Jun 30 2018

Grinshtein N et al. identified key epigenetic modulators in GBM that regulate BTIC growth and survival and highlight promising combination therapies. [Read the Full Post]

Therapeutic effects of histone deacetylase inhibitors in a murine asthma model

788 | 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

816 | 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

884 | 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

778 | 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

1033 | 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

889 | Jun 15 2018

Wang Z et al. explained the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. [Read the Full Post]

Human Papillomavirus Downregulates the Expression of IFITM1 and RIPK3 to Escape from IFNγ- and TNFα-Mediated Antiproliferative Effects and Necroptosis

1200 | Jun 12 2018

Ma W et al. revealed how hrHPV deregulates two pathways involved in cell death and growth regulation to withstand immune-mediated control of hrHPV-infected cells. [Read the Full Post]

Impairment of hypoxia-induced HIF-1α signaling in keratinocytes and fibroblasts by sulfur mustard is counteracted by a selective PHD-2 inhibitor

2069 | Jun 10 2018

Deppe J, et al. described a pathomechanism by which SM negatively affects hypoxia-stimulated HIF-1α signaling in keratinocytes and fibroblasts and thus possibly contributes to delayed wound healing in SM-injured patients that could be treated with PHD-2 inhibitors. [Read the Full Post]

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

1453 | Jun 10 2018

Szczepanowicz K et al. indicated the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity. [Read the Full Post]

Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation

484 | Jun 09 2018

McCullough CE et al. pointed to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys-274 autoacetylation for subsequent cognate substrate acetylation. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

0 | Jun 07 2018

Hu L et al. indicated that IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins

460 | Jun 01 2018

Li R et al. provided evidence for an anti-proliferative role of Ulk1 in response to Hsp90 inhibition in cancer cells. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | May 12 2018

Yun T et al. found that HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta

1318 | May 08 2018

Zuo R et al. found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. [Read the Full Post]

Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation

751 | May 06 2018

Wang M et al. illustrated two divergent pathways mediating a continuous increase of DNA methylation and also sheds further light on the epigenetic basis for single-cell differentiation in plants. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1269 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1

677 | Apr 20 2018

Zhang Z et al. provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

2557 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice

941 | Apr 04 2018

Sun Q et al. suggested that fisetin has a therapeutical potential for treating ALD. [Read the Full Post]

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition

1204 | Apr 03 2018

Tse AK et al. illustrated a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

0 | Mar 30 2018

Tang X et al. demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. [Read the Full Post]

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation

1135 | Mar 24 2018

van de Ven AL et al. suggested that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCAmutations, such as those with PTEN and TP53 deletions. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

1559 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1267 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

1186 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells

819 | 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

1295 | Mar 10 2018

Terranova-Barberio M et al. suggested that the combination of HDACi (e.g., VPA) and capecitabine is an innovative antitumor strategy that warrants further clinical evaluation for the treatment of metastatic breast cancer. [Read the Full Post]

Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines

1095 | Feb 14 2018

Jane EP et al. provided a new insight into the link between Bcl-xL and survivin inhibition for the development of novel therapies for glioma. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

2273 | Feb 14 2018

You M et al. provided molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

Reprogramming of histone methylation controls the differentiation of monocytes into macrophages

557 | Feb 13 2018

Zheng QF et al. elucidated mechanisms crucial to the dynamic establishment of epigenetic memory, which is central to the maintenance of the MP differentiation blockade. [Read the Full Post]

Fibroblast Growth Factor 21 (FGF21) Promotes Formation of Aerobic Myofibers via the FGF21-SIRT1-AMPK-PGC1α Pathway

559 | Feb 07 2018

Liu X et al. revealed a novel mechanism of myogenesis and muscle fiber transformation and indicated that FGF21 serves as a vital regulator of muscle development and important contributor to the pathogenesis of myopathy. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

2244 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

584 | Feb 05 2018

Grandy RA et al. established a new dimension of chromatin regulation important in the maintenance of pluripotency. [Read the Full Post]

Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney

578 | Feb 04 2018

Cai M et al. concluded that glucose is a potent inducer of histone acetylation and methylation, which in turn leads to upregulation of OPN gene expression. Treatment targeting histone marks may therefore represent an alternative method to protect kidneys from deleterious effects of glucose. [Read the Full Post]

A novel HDAC6 inhibitor Tubastatin A: Controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses Temozolomide-induced ER stress-tolerance in GBM cells

1604 | Jan 27 2018

Li ZY et al. showed that the balance of HDAC6-p97/VCP was crucial to ERST-associated TMZ resistance and that HDAC6 inhibition might be a synergistic target and strategy along with TMZ for the improvement of clinical glioma treatment. [Read the Full Post]

Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma

977 | Jan 16 2018

Liu F et al. provided a solid evidence for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC. [Read the Full Post]

CK1δ kinase activity is modulated by protein kinase C α (PKCα)-mediated site-specific phosphorylation

2423 | Jan 14 2018

Meng Z et al. contributed to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. [Read the Full Post]

Concomitant BET and MAPK blockade for effective treatment of ovarian cancer

669 | Jan 08 2018

Jing Y et al. supportted concomitant BET and MAPK blockade as an effective therapeutic strategy in ovarian cancer. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | Jan 03 2018

Yun T et al. induced p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

2730 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways

1244 | Dec 26 2017

Ni L et al. provided a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan. [Read the Full Post]

G-quadruplex-based fluorometric biosensor for label-free and homogenous detection of protein acetylation-related enzymes activities

1006 | Dec 26 2017

The potency of this assay is further demonstrated by detecting HAT/HDAC activity in cell lysates and evaluating HAT and HDAC-targeted inhibitors, C464 and EX 527, respectively. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

1479 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1

1524 | Dec 23 2017

Wang L et al. found the potential clinical significance, as a large proportion of patients could be at risk of developing severe toxicity if irinotecan is co-administered with belinostat. [Read the Full Post]

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL

1166 | Dec 19 2017

Hasanov E et al. identified VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. [Read the Full Post]

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

1032 | Dec 11 2017

Maimaiti Y, et al. indicated that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer. [Read the Full Post]

Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

1128 | Dec 02 2017

Peters TL et al. characterized recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. [Read the Full Post]

The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb

753 | Nov 27 2017

Lu P et al. suggested that the BET inhibitor OTX015 may be a candidate for anti-HIV-1-latency therapies. [Read the Full Post]

Kinome Profiling Identifies Druggable Targets for Novel Human Cytomegalovirus (HCMV) Antivirals

694 | Nov 26 2017

Arend KC et al. showed the utility of MIB-MS kinome profiling for identifying existing kinase inhibitors that can potentially be repurposed as novel antiviral drugs. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

1537 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

Targeting protein kinase C in mantle cell lymphoma

1189 | Nov 16 2017

Rauert-Wunderlich H et al. showed that MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

742 | Nov 12 2017

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

1841 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

650 | Nov 04 2017

Chen D et al. suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

0 | Oct 29 2017

Noguchi K et al. suggested that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

1009 | Oct 28 2017

Yalon M et al. showed that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. [Read the Full Post]

ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli

1384 | Oct 22 2017

Siddharth S et al. showed that increased APC physically interacts with PARP-1 and inhibits PARylation causing the non assembly of base excision repair (BER) multiprotein complex, resulting in an irreparable DNA damage and subsequent apoptosis. Knockdown of APC in mBCSCs inhibited DNA damage, increased BER and PARylation, reduces apoptosis while the over-expression of APC in BT20 (APC low expressing) cells reversed the effect. Thus, combination of QC and ABT-888 decreased mBCSCs growth by activating APC and inhibiting BER within the cells. [Read the Full Post]

Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer

1353 | Oct 20 2017

Cardillo TM et al. demonstrated the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

0 | Oct 11 2017

Chang X et al. reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

3355 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

0 | Oct 09 2017

Eyer L, et al. suggested that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

0 | Oct 09 2017

Eyer L, et al. suggested that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

0 | Oct 06 2017

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

Inhibition of Extracellular Calcium Influx Results in Enhanced IL-12 Production in LPS-Treated Murine Macrophages by Downregulation of the CaMKKβ-AMPK-SIRT1 Signaling Pathway

1150 | Oct 05 2017

Liu X et al. demonstrated a new role of transmembrane calcium mobilization in immunity modulation such that inhibition of calcium influx leads to impaired activation of CaMKKβ-AMPK-SIRT1 signaling pathway which lifts restriction on NF-κB activation and results in enhanced IL-12 production. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Mohseni J et al. established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines.

1410 | Sep 17 2017

Pinkerneil M et al. combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

0 | Sep 16 2017

Mohseni J et al. showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Inhibition of PRMT5 suppresses osteoclast differentiation and partially protects against ovariectomy-induced bone loss through downregulation of CXCL10 and RSAD2

690 | Aug 29 2017

Dong Y et al. found that PRMT5 is an activator of osteoclast differentiation and inhibition of PRMT5 partially suppressed osteoclastogenesis through downregulation of CXCL10 and RSAD2. [Read the Full Post]

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

999 | Aug 28 2017

Li Q et al. revealed that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). [Read the Full Post]

Leptin-STAT3-G9a Signaling Promotes Obesity-Mediated Breast Cancer Progression

840 | Aug 28 2017

Chang CC et al. showed how targeting STAT3-G9a signaling regulates CSC plasticity during obesity-related breast cancer progression, suggesting a novel therapeutic paradigm to suppress CSC pools and limit breast malignancy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

1602 | 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

1579 | 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

1644 | 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

1850 | Aug 23 2017

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

2112 | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

2310 | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

718 | Aug 08 2017

Han T et al. suggested that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

1393 | Jul 31 2017

Noguchi K et al. suggests that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

1240 | Jul 30 2017

Katsha A et al. indicated that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA-EIF4E-c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways.

0 | Jul 29 2017

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways.

0 | Jul 22 2017

Ghosh R et al. highlighted specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

1770 | 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

1954 | Jul 19 2017

Imai Y et al. findings underscore the usefulness of calcineurin-targeted therapy in MM patients, including patients who are resistant to bortezomib. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

2172 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

0 | Jul 07 2017

Buoncervello M et al. opened a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

1907 | Jun 26 2017

Nunn AD et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5192 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

1807 | Jun 12 2017

Bi G et al. found that PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

3074 | Jun 11 2017

Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells

1564 | Jun 10 2017

Vanden Heuvel JP et al. found that cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. [Read the Full Post]

The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line

1689 | Jun 02 2017

Wang J et al. found that serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

The Promoting Effect of Radiation on Glucose Metabolism in Breast Cancer Cells under the Treatment of Cobalt Chloride

1809 | May 27 2017

Zhao CB et al. found that the combination of radiation and hypoxia could promote the glucose metabolism. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2538 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3

0 | May 24 2017

Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

0 | May 23 2017

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2298 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

0 | May 12 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 10 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.

0 | May 10 2017

Those results improve Li Det al.'s understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 09 2017

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1655 | May 02 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

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

0 | May 01 2017

de Andrade PV et al demonstrate that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

2967 | Apr 30 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1595 | Apr 25 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

1342 | Apr 22 2017

Lakatos P et al. found that PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2324 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

0 | Apr 06 2017

Hsu YC et al showed that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. [Read the Full Post]

Activation of the miR-34a/SIRT1/p53 Signaling Pathway Contributes to the Progress of Liver Fibrosis via Inducing Apoptosis in Hepatocytes but Not in HSCs

1492 | Apr 04 2017

Tian XF et al. found that the miR-34a/SIRT1/p53 signaling pathway might be a promising therapeutic target for liver fibrosis. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Mar 23 2017

Meng Z et al indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2252 | Mar 14 2017

Tsunoda K et al. suggested that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

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

2972 | Mar 13 2017

Fang M et al revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

0 | Feb 28 2017

Ma HT, et al.'s results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeuticmediated cell death

1558 | Feb 27 2017

Chen H, et al.'s results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

0 | Feb 17 2017

When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. [Read the Full Post]

NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

962 | Feb 13 2017

Hu P, et al.‘s ’ study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

0 | Feb 12 2017

Jian Y, et al.'s study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1225 | Feb 02 2017

These evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways

1232 | Feb 02 2017

Guan JH et al. revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

2800 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

2418 | Jan 27 2017

Meng Z et al. found that non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2483 | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death

1712 | Jan 15 2017

Chen H et al. found the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

1768 | Jan 15 2017

Ma HT et al. provided a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2550 | Jan 05 2017

Jian Y, et al.'s our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

1229 | Jan 05 2017

Hu P, et al.‘'s study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

1135 | Dec 29 2016

The study of Guan JH, et al. primarily revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1385 | Dec 28 2016

Zhang W, et al.'s evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

2127 | 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

2522 | Dec 22 2016

The findings of Buoncervello M et al. open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways

1954 | Dec 14 2016

Ghosh R et al.'s findings highlight specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients.

0 | Nov 29 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J, et al have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines

2396 | 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

3514 | 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

2506 | Nov 24 2016

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

1871 | Nov 23 2016

Nucleoside Inhibitors of Zika Virus

1172 | Nov 20 2016

Antiviral activity was identified when 2'-C-methylated nucleosides were tested, suggesting that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

1805 | Nov 17 2016

Chang X et al. revealed that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

1836 | Nov 11 2016

Yalon M et al. found that drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.

2410 | Nov 08 2016

Davis MR, et al. found that The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. [Read the Full Post]

Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines

1996 | Nov 02 2016

Hegde M et al. revealed that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity. [Read the Full Post]

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

2469 | Oct 31 2016

Shinde V, et al. found that the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. [Read the Full Post]

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

2593 | Oct 28 2016

[Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

4884 | Oct 27 2016

Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3'-monoxime

2145 | Oct 21 2016

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

2583 | Oct 20 2016

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3

2696 | Oct 09 2016

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer

2418 | Oct 09 2016

Li D et al. improved the understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

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

2369 | Sep 28 2016

De Andrade PV et al demonstrated that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

No Significant Cytotoxic Effect of the EZH2 Inhibitor Tazemetostat on Pediatric Glioma Cells with Wildtype Histone 3 or Mutated Histone 3.3

1153 | Sep 18 2016

Wiese M et al. suggested that EZH2 inhibition might not offer an effective single agent treatment option for paedHGG patients. However, the therapeutic efficacy in combination with cytotoxic and/or other epigenetically active agents still has to be elucidated. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2015 | Sep 09 2016

Hsu YC et al. identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. [Read the Full Post]

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

3969 | Sep 02 2016

Fang M, et al. revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

The interferon-related developmental regulator 1 is a key factor for human papillomavirus-induced NFкB inhibition

4601 | 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

4835 | 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

8769 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Histone deacetylase inhibitors have negative effects on the elimination of HIV-infected cells by cytotoxic T-Lymphocytes

4666 | Mar 02 2015

Jones et al. tested the impact of three HDACis, suberanilohydroxamic acid (SAHA), romidepsin and panobinostat, in clinical development on immune effectors functions, such as T-cell effector. [Read the Full Post]

An inverse correlation between homologous recombination and Polθ in epithelial ovarian cancers

3849 | Feb 27 2015

Ceccaldi et al. reported that HR activity inversely correlated with Polθ expression in EOCs. [Read the Full Post]

The combination of broadly neutralizing antibodies and viral inducers can suppress the establishment of HIV-1 latent reservoir

5783 | Feb 13 2015

Halper-Stromerg et al. demonstrated that broadly neutralizing antibodies (bNAbs) can suppress the establishment of a silent reservoir in humanized mice. [Read the Full Post]

Star27 overcomes synthetic lethal toxicity for FLT3-targeted therapy against acute myeloid leukemia

4460 | Feb 06 2015

For overcoming myelosuppression, Warkentin et al. reported a staurosporine analog, Star27, that enable to inhibit FLT3 while avoiding KIT inhibition. [Read the Full Post]

Recently identified CHEK2 Y390C mutation facilitates early breast cancer development

6206 | Feb 05 2015

Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. [Read the Full Post]

The distribution of primary cilia in the mouse embyo

4582 | Jan 27 2015

Bangs et al. demonstrate the time and location that primary cilia appear in the mouse embryo. [Read the Full Post]

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

4539 | 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

4803 | 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

6148 | 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]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

6350 | Jan 14 2015

Nishimura et al. revealed that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

11204 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

Resvertrol targets a human tRNA synthetase for activation of NAD+-dependent PARP1

4912 | Jan 05 2015

Mathew Sajish and Paul Schimmel found resvertrol interacts with tyrosyl transfer-RNA (tRNA) synthetase (TyrRS), which translocates to the nucleus in response to stress, to initiating its effect in nuclear. [Read the Full Post]

Cep68 act as an important linker protein of centrosomes and centriole disengagement

4591 | Dec 26 2014

Pagan et al. indentified the important roles of Cep68 and other related factors during the disengagement of centrosomes and entrioles. [Read the Full Post]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

7878 | Dec 17 2014

By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of JAK signaling were able to convert white adipocytes to brown adipocytes. [Read the Full Post]

The inhibition of BET leads to a suppression of osteoclastogenesis

2893 | Dec 15 2014

Park-Min et al. found the inhibitor of bromo and extra-terminal (BET), I-BET151, can strongly reduce osteocelstogenesis. [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

6513 | 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]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

8027 | 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]

Quickly switching of spindle checkpoint states is due to negative feedback at kinetochrores

4115 | Nov 27 2014

Nijenhuis et al. found this phenomenon arises due to localized negative feedback of spindle assemble checkpoint (SAC) signal, which ensure kinetochres switch SAC signalling OFF rapidly. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

10098 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

The combination of metformin and conventional tuberculosis drug as a new therapeutic strategy

2694 | Nov 20 2014

Singhal et al. demonstrated a diabetic drug, metformin (MET), mediates host cell responses to pathogen for promoting anti-Mtb activities. The combined regimens have shown promising positive clinical effects on tuberculosis patients.The article was published on Science Translational Medicine. [Read the Full Post]

Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion

8120 | Nov 10 2014

Rachel R. Stine et al. found Slit-Robo and JAK-STAT signaling pathways play key roles in stem cells competition within their niches. [Read the Full Post]

High-fat diet and NAD+ replenishment can rescue Cockayne Syndrome

5217 | Nov 07 2014

Scheibye-Knudsen et al. demonstrated high-fat diet, the inhibition of β-OHB, and the elevation of NAD+ levels, may have the effect to rescue CS-associated phenotype through activating SIRT 1 signaling. [Read the Full Post]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

6620 | Nov 03 2014

Megakaryopoiesis is regulated by TPO, which activates multiple signaling molecules. Besancenot et al. demonstrated that the protein levels of JAK2 and MPL determine TPO-induced megakaryopoiesis. [Read the Full Post]

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

5234 | 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]

PCI34051 is a potent histone deacetylase 8 inhibitor

3937 | 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]

AZD2281 is an experimental chemotherapeutic agent

3860 | Feb 27 2014

Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM [Read the Full Post]

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

3846 | Feb 25 2014

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

SB939 is a novel histone deacetylase inhibitor with improved

3976 | 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]

MS 275 is a benzamide histone deacetylase inhibitor undergoing clinical trials

3974 | 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

3861 | 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]

WP1066 is a cell permeable AG 490 tyrphostin analog

6017 | Jan 15 2014

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. [Read the Full Post]

SB939 is a novel histone deacetylas inhibitor with improved

3881 | 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]

ABT 888 is a potential anti cancer drug acting as a PARP inhibitor

4297 | Dec 20 2013

ABT-888 is inactive to SIRT2 (>5 μM) .ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. [Read the Full Post]

Givinostat is a histone deacetylase inhibitor with potential

3515 | 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]

Olaparib is an experimental chemotherapeutic agent

0 | Dec 12 2013

Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. [Read the Full Post]

CUDC 101 is a potent inhibitor of histone deacetylase

3694 | 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]

AG 014699 is a PARP inhibitor being investigated as a potential anti cancer agent

4097 | Nov 21 2013

Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. [Read the Full Post]

BMN 673 was generally well tolerated

4019 | Nov 08 2013

BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. [Read the Full Post]

Olaparib is an experimental chemotherapeutic agent

3812 | Nov 07 2013

Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). [Read the Full Post]

BMN 673 is an orally bioavailable inhibitor of the nuclear

3419 | Nov 04 2013

BMN 673 is a novel PARP inhibitor with IC50 of 0.58 nM. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. [Read the Full Post]

SB939 is a pan histone deacetylase inhibitor binding

3752 | 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]

This study is designed to evaluate the efficacy and safety of tofacitinib

6661 | Oct 30 2013

Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. [Read the Full Post]

IOX2 is a potent inhibitor of HIF 1 prolyl hydroxylase 2 with IC50

4358 | Oct 29 2013

IOX2 potently inhibits PHD2 (IC50 of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. [Read the Full Post]

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

3561 | 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]

Veliparib is a potential anti cancer drug acting as a PARP inhibitor

0 | Oct 09 2013

ABT-888 is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM, respectively. It is inactive to SIRT2. [Read the Full Post]

Staurosporine is a potent PKC inhibitor with IC50

5389 | Sep 24 2013

Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. [Read the Full Post]

MS275 strongly inhibits HDAC1 and HDAC3 with IC50

3499 | Aug 29 2013

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

Veliparib is a potential anti cancer drug acting as a PARP inhibitor

3411 | Jun 17 2013

ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. [Read the Full Post]

Rucaparib is a PARP inhibitor being investigated as a potential anticancer agent

3210 | May 20 2013

Rucaparib also reduces the migration of some cancer and normal cells in culture.It can be taken orally in tablet form. [Read the Full Post]

Tubastatin A was substantially more selective than the known HDAC6 inhibitor

3736 | 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]

IOX2 is a potent inhibitor of HIF1with IC50 of 21 nM

4208 | Apr 16 2013

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

3603 | 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]

AEB071 is a potent selective pan PKC inhibitor

4232 | Jan 16 2013

Multiple sclerosis is a chronic and debilitating immune-mediated disease of the central nervous system . Recent epidemiological data supports the established view that the incidence of AEB071 MS peaks at about 30 years of age and that it is a disease with a positive female-to-male ratio. [Read the Full Post]

Activation of the HIF pathway in cancer

4319 | Dec 20 2012

nhibiting c-MET (mesenchymal_epithelial transition factor) signaling is emerging as a promising strategy for a new class of targeted cancer therapies. Several c-MET inhibitors are in various stages of clinical development and have demonstrated activity in different tumor HIF pathway types. [Read the Full Post]

PKC Inhibitors is associated with endothelial dysfunction

4213 | Dec 06 2012

Atherosclerosis is initiated by the deposition, retention and oxidative modification of apolipoprotein (apo)B-containing lipoproteins, notably low-density lipoprotein cholesterol (LDL-C) in the vessel wall. This is associated with endothelial PKC Inhibitors dysfunction and recruitment of monocytes that take up oxidised LDL to become macrophage-derived foam cells, collectively apparent macroscopically as "fatty streaks". [Read the Full Post]

HDAC is also shown to occur in an inhibitor

3966 | 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]

PARP INHIBITOR: STROKE ISCHEMIA AND CANCER

3913 | Sep 27 2012

DEREGULATION OF PARP CASCADE: In humans, Poly (ADP-ribose) polymerase or PARP enzymes are encoded by PARP gene and regulate some crucial processes in the cells for example programmed cell death or the DNA repair system. They play their role in DNA repair process by repairing the ssDNA or single stranded DNA breaks on DNA. The interaction of BRCA1 and BRCA2 with them is very well documented which links the deregulation of PARP with ovarian and breast cancer because many of these types of cancers are associated with the mutations in BRCA1 and BRCA2 genes. For this reason, the inhibition of PARP is found to be an attractive therapeutic approach due to the specificity and effectiveness of PARP specific inhibitors against the cancers caused by BRCA genes. An inhibitor having specificity for PARP exhibits good results due to high sensitivity of cancer cells against PARP inhibiting drugs leaving the healthy cells unaffected. Hence the PARP inhibition mechanism has made them an attractive and better choice as compared to the conventional therapies affecting all the healthy cells as well. [Read the Full Post]

VORINOSTAT: A HYDROXAMIC ACID

4476 | 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]

PARP INHIBITOR: TREATMENT OF STROK, ISCHEMIA AND CANCER

3294 | Sep 09 2012

DEREGULATION OF PARP CASCADE AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are the translated product of PARP genes located in human genome. These proteins play some of the vital roles in the cell such as apoptosis and DNA repair mechanism. The repair mechanism of DNA is specific for the single stranded DNA (ss DNA) breaks. A reasonable work has been reported about the interaction of BRCA1 and BRCA2 and this knowledge leads to the understanding of PARP deregulation causes or links with ovarian and breast cancer as different research reports concluded the mutations of these two genes are present in these cancers. Due to these reasons the PARP inhibition mechanism has become an efficient therapeutic tool for cancer treatment [1]. The specific PARP inhibitors may have efficient results against tumors and cancers with BRCAness. The beauty of these PARP inhibitors is that the normal cells are not affected where tumors cells are only targeted. Mechanism of PARP inhibitor tells about the efficacy of these inhibitors in treatment of cancers and because of their efficient actions the old therapies are becoming less popular as they affect the normal cells as well. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS BEYOND CANCER TREATMENT

4083 | 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]

HDAC INHIBITORS AGAINST TOMORS

4333 | 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

4082 | 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

3938 | 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]

PARP INHIBITOR: A MULTI PURPOSE AGENT

3539 | Jul 23 2012

PARP INHIBITOR AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are translated by the PARP genes which are a part of human genome. PARP are vital proteins for some of the most important functions such as DNA repair mechanism and apoptosis. There are many reports of research in which a close relation of PARP inhibition is noted with BRCA1 and BRCA2 which are associated with onset of ovarian and breast cancer. Based on these research reports PARP inhibition has become a novel tool for the treatment of different types of cancers and tumors. PARP inhibitors have shown efficient results against BRCA genes. PARP protein inhibitor has unique property of not affecting normal cell; therefore these inhibitors are specific for cancer cells. The choice for cancer treatment with least side effects is becoming famous due to PARP inhibitors which are potent anti cancer agents. [Read the Full Post]

PARP INHIBITOR: A THERAPEUTIC AGENT FOR ISCHEMIA, STROK AND CANCER

3596 | Jul 15 2012

USES OF PARP INHIBITOR AND DOWNREGULATION OF PARP CASCADE Human genome consists of different genes one of which is PARP gene which translates to produce PARP or Poly ADP-ribose polymerases. Important functions of cells like programmed cell death and mechanism of DNA repair is being controlled by these proteins. Breaks in single strand of DNA are specifically repaired by these proteins. Since BRCA1 and BRCA2 are involved in breast and ovarian cancer onset their associations with PARP inhibition have been reported in a number of researches. Because of these details inhibition of PARP has become a vital tool for therapy of various cancers [1]. Against these BRCA genes inhibitors of PARP have shown effective results. PARP inhibitors specifically targets only the cancer cells not normal cells which is their edge point. Conventional therapies have become less famous because mode of action of PARP inhibitor has shown that it is very good against different cancers. [Read the Full Post]

INHIBITORS OF HISTONE DEACETYLASE

3255 | 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]

PARP INHIBITOR: TREATMENT OF STROK, ISCHEMIA AND CANCER

3320 | Jul 08 2012

DEREGULATION OF PARP CASCADE AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are the translated product of PARP genes located in human genome. These proteins play some of the vital roles in the cell such as apoptosis and DNA repair mechanism. The repair mechanism of DNA is specific for the single stranded DNA (ss DNA) breaks. A reasonable work has been reported about the interaction of BRCA1 and BRCA2 and this knowledge leads to the understanding of PARP deregulation causes or links with ovarian and breast cancer as different research reports concluded the mutations of these two genes are present in these cancers. Due to these reasons the PARP inhibition mechanism has become an efficient therapeutic tool for cancer treatment. The specific PARP inhibitors may have efficient results against tumors and cancers with BRCAness. The beauty of these PARP inhibitors is that the normal cells are not affected where tumors cells are only targeted. Mechanism of PARP inhibitor tells about the efficacy of these inhibitors in treatment of cancers and because of their efficient actions the old therapies are becoming less popular as they affect the normal cells as well. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – CANCERS AND BEYOND

4226 | 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]

PARP INHIBITOR: ISCHEMIA, STROK AND CANCER

3963 | Jun 24 2012

PARP CASCADE DEREGULATION AND ITS IMPLICATION: PARP are Poly ADP-ribose polymerases and translated by PARP genes present in human genome. These proteins are important for the regulation of critical processes such as DNA repair mechanism and programmed cell death. The DNA repair mechanism based on these enzymes is specific for ssDNA (single stranded DNA) breaks. A sufficient data is available on the BRCA1 and BRCA2 interaction which leads to the concept of PARP deregulation link with breast and ovarian cancer because many cases of these cancers reported about the mutations present in these two genes. Because of this reason PARP inhibition mechanism has proved as an effective therapeutic tool [1] where inhibitors specific for PARP may have effective results against cancers and tumors with BRCAness. PARP inhibitors are mostly specific as the tumor cells are targeted by these molecules therefore the normal cells remain un-affected. The mechanism of PARP inhibitor is so effective against cancer and due to this reason conventional therapies are becoming less useable due to their effects on healthy cells as well. [Read the Full Post]

VORINOSTAT: THE FAMOUS HYDROXAMIC ACID

3620 | 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]

PARP INHIBITOR: CANCER, ISCHEMIA AND STROKE

2906 | May 15 2012

IMPLICATION OF DEREGULATION OF PARP CASCADE: PARP or Poly ADP-ribose polymerase enzymatic proteins are encoded by PARP genes in human, and are responsible of regulating the critical cellular processes for example, programmed cell death and DNA repair channel. They play their role in DNA repair pathway by repairing the single-stranded DNA breaks (ssDNA). The interaction of BRCA1 and BRCA2 with them is very well documented that describes a link between PARP deregulation and ovarian and breast cancer, as many among these cancers are associated with the mutations inside these two genes. This is why the PARP inhibition process has proved to be an attractive therapeutic tool [1] and PARP specific inhibitor molecule may prove highly effective against tumors with BRCAness. Generally PARP selective inhibitor exhibits good results due to the tumor cells beings highly sensitive for PARP inhibitor drug leaving the remaining healthy cells. Hence PARP inhibitor mechanism has made them a better choice as compare to the conventional therapies that must affect all the cells irrespective of their status. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3478 | 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]

VORINOSTAT – AN ANTI HISTONE MODIFYING AGENT

3527 | 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

3198 | Apr 16 2012

STAUROSPORINE: A PKC INHIBITOR

5812 | Mar 25 2012

STAUROSPORINE PROPERTIES AND ORIGIN: The discovery of Staurosporine was done during the research on a bacterium Streptomyces staurosporeus in 1977, this compound was identified as an antibiotic and now this molecules has been studied thoroughly. Another alternate name of this molecule is STS or Staurosporine AM-2282, its configuration and structure was identified by certain physical techniques such as analysis of X-ray. Staurosporine PKC inhibitor is also found as active against a good number of protein kinases (PKs), Staurosporine IC50 for PKA, PKC and PKG is 7.0 nM, 0.7 nM and 8.5 nM respectively. When Staurosporine is stored at -20 oC it’s stability remains un-affected for two years. This compound is soluble in DMSO. Molecular weight of Staurosporine is 466.53 and it is expensive as Staurosporine price for 1 mg is more than $500, however the price is variable from one Staurosporine supplierto other. Staurosporine PKC inhibitor is available easily and if someone wants to purchase Staurosporine for laboratory and research use one can buy Staurosporine easily. [Read the Full Post]

OLAPARIB: THE FIRST PARP INHIBITOR

4580 | Mar 19 2012

Introduction: PARP Inhibition Signaling activities within the cell are conducted along set pathways of protein – protein interactions. Depending on the cell status and the ligands triggering the signaling cascade to what function is carried out in the nucleus. A protein located in the nucleus has been established to be the principle regulator of the apoptosis and repair functions of certain DNA damage. This protein is called “Poly (ADP-ribose) polymerase” or it is abbreviated to “PARP”. The PARP family of proteins is extensive with 17 members currently known and the range of effects of PARP activity is large. The general structure of the PARP series of proteins contains four different types of binding domains which dictate the activity, one of the domains is referred to as the catalytic domain contains an amino acid sequence that is identical between all the members of the protein family. The mechanism of action of PARP proteins is to add a series of ADP ribose molecules to the protein ligands, the number and site of this addition controls the response of the affected protein. [Read the Full Post]

PANOBINOSTAT

5054 | 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

3751 | 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

3466 | 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

3697 | 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]

CP-690550: THE CURE FOR ARTHRITIS

6316 | Mar 20 2012

Introduction: JAK and its role in signaling pathways The protein kinase family plays an essential role in the government of the growth or death properties of mammalian tissues. These proteins form an interrelated, redundant system that is capable of selectively initiating the growth of certain cell types in response to the needs of the host system. To do this the protein kinase super family is subdivided into a series of related protein kinases which make up a signaling pathway, traveling from the extracellular matrix into the cell nucleus. The Janus kinase pathway is one which is activated in response to the action of cytokines on the cytokine transmembrane receptors. Since these receptors have no kinase ability themselves they are total dependant on the Janus kinases (JAK) for activity. [Read the Full Post]

ENZASTAURIN AGAINST MALIGNANCIES

3769 | Mar 20 2012

Introduction: The Protein Kinase C family A cytosolic protein kinase isolated in the late 1970’s by the Nishizuka group of Kobe University, Japan has been found to be a key factor in the regulation of the cell cycle. Established as the protein kinase C family several isoforms have subsequently be isolated. These serine / threonine kinases are activated by the diacylglycerol (DAG) which is generated by the agonist induced hydrolysis of Trans-membrane G-protein kinases or tyrosine kinases. Activation of protein kinase C leads to a movement of the protein to the either the cytosolic skeleton or to the cellular membrane triggering a cascade of downstream signals which induce cell growth, differentiation or proliferation activities, this process appears to be mediated by the release of Ca2+. One of the key elements to be discovered concerning this protein was the discovery that phorbol esters were also a ligand for activating this protein; this created a direct link between PKC and the formation of various tumors. [Read the Full Post]

INCB18424 – JACKING THE JAK2

7005 | Mar 20 2012

Introduction: JAK2 in relation to metabolic blood disorders The transmission of signals from extracellular factors through the cell membrane to effect actions within the cell cytosole and nucleus is conducted along pathways of protein to protein interactions. Many metabolic disorders have been associated with aberrations in these pathways causing a variety of destructive cellular actions. Many of these diseases possess no known cure and in response research has focused on the mechanisms behind the progression of these diseases. One area that has received a lot of attention is the possibility that the natural immune function can be detrimental to healthy growth patterns if over stimulated by mutations in the genetic information of individuals. A key series of proteins in the immune response is the Janus kinases (JAK), a series of four distinct but domain related kinases located in the cellular cytosole. These kinases form a distinct link between extracellular immune function ligands and a direct regulation of transcription of genetic information. However, a mutation of the JAK2 isoform has been associated with degenerative effects such as myeloproliferative neoplasms, thrombocythemia, polycythemia vera and psoriasis. [Read the Full Post]

PARP INHIBITOR IN CANCER, STROKE AND ISCHEMIA

2942 | Mar 18 2012

Introduction: Mechanism of Action of Poly (ADP-ribose) polymerase (PARP) Within any cellular growth process there must be facilities for the replication of DNA, however, this process is not always 100% accurate. In addition mechanisms for the repair of incorrect sequences or the repair of cytotoxic damaged DNA must exist in tandem. PARP is not part of a repair mechanism but it does function as one of the regulatory enzymes controlling the mechanisms that do repair DNA such as the BER/SSER pathway. As well as regulating DNA repair PARP is a true multi-tasking protein since it also regulates the normal processes of cell disposal (ie cell death, apoptosis), development of neuro-functions and many other cell proliferation processes. PARP is typically located in the cell nucleus where in combination with other proteins recognizes minor DNA strand damage, forms skeletal structures around the site of the damage and enrolls specific proteins to remove the damaged section and replace the missing part. [Read the Full Post]

U0126: THE MOST POTENT MEK INHIBITOR

5303 | Mar 18 2012

The MAPK pathways In ever cells life span there are circumstances when the cell is placed in a stressful situation, such toxic shock, injury to the surrounding tissue or old age. In such circumstances the cells must react either to die or to live and grow. The regulation of this process is the responsibility of the “Mitogen-activated protein kinases (MAPK)”. The MAP kinases are involved in a broad spectrum of processes covering proliferation (mitosis), apoptosis, cell migration/motility and gene expression. The MAP kinases are located in the cell membrane and on receipt of an external extracellular signal any one of three pathways can be stimulated, these are the ERK, JNK or the P38MAPK pathways. [Read the Full Post]

TASOCITINIB: THE REVOLUTION IN ARTHRITIS MANAGEMENT

6680 | Mar 18 2012

Introduction: Inhibition of the JAK pathway The protein kinases are a super family of protein that govern the control of cellular growth, creation of vascular structure and many other processes the control the way in which cells and tissue regenerate. In is estimated that 30% of all cellular regulation is governed by protein kinases. Protein kinases are subdivided into 7 different classifications of which one is the tyrosine kinases. These kinases operate by phosphorylation of a tyrosine amino acid residue transferring a signal down a cascade of protein to regulate cellular processes. A further subdivision of the tyrosine kinases can be made into receptor based kinases and non receptor based kinases. The Janus kinases (JAK) are a sub family of the receptor based tyrosine kinases. Signals from the JAK regulate the cytokines, the GM-CSF family and the GP130 receptor family. JAK kinases exist in the 4 distinct isoforms with twinned phosphorylation domains. Inhibitors of the JAK kinases have been demonstrated to have a positive effect on cancerous cells both in vivo and in vitro. [Read the Full Post]

HDAC INHIBITOR AND ITS EEFICACY IN CANCER

3257 | 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]

OLAPARIB FOR PARP-1 INHIBITION

4048 | Mar 13 2012

PARP-1 Inhibition and its Implications in Cancer: The Poly [ADP-ribose] polymerase 1 or PARP-1 proteins have been well documented to be linked with cancers affecting their differentiation, proliferation and transformation. On the other hand, BRCA1 and BRCA2 genes are also well linked with the highly proliferating ovarian and breast cancer and hence the development of PARP-1 inhibitors that can target the aforementioned genes effectively in breast and ovarian cancer cells has been considered as a very attractive and feasible approach. The increasing popularity of PARP-1 inhibitors can be attributed to their specific action against cancer cells while sparing normal cells. [Read the Full Post]

AZD1152 – AN AURORA KINASE INHIBITOR

5456 | Mar 13 2012

Inhibition of AURORA KINASES in relation to cancer: Mitosis is a key process in the regeneration of cellular material and two key regulators of this function are serine and threonine kinases which are more commonly known as Aurora Kinases. Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin, have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). [Read the Full Post]

RUXOLITINIB: THE JACK FOR JAK INHIBITION

6859 | Mar 13 2012

Ruxolitinib: Inhibition of the Janus Kinases The janus kinases are a sub family of the protein kinases and are refer to as non receptor tyrosine kinases. Signals from the Janus kinases regulate several different types of proteins such as the cytokine receptor family (interferon), the GM-CSF family and the GP130 receptor family. The JAK kinases occur in four isoforms, with two matching phosphorylation domains, one for activity one for regulation. JAK2 in been shown to be mutated in several conditions including thrombocthemia and myeloprliferation disorders. In relation to haematological maliganacies the JAK2 mutation have been shown to essential for tumor growth and proliferation. Inhibiting the JAK2 kinase offers a potential mechanism for chemotherapeutic action. Ruxolitinib is a small, molecule inhibitor that has been established to inhibit the Janus kinases; early clinic work established that Ruxolitinib has sufficient anti-tumor activity to warrant further investigation. [Read the Full Post]

AZD2281: THE FIRST PARP INHIBITOR

3988 | Mar 13 2012

Introduction: PARP Inhibition Poly (ADP-ribose) polymerase (PARP) is an enzyme located in the cell nucleus that regulates apoptosis and controls repair of minor damaged DNA strands. Since DNA mutations are a common function of many clinical diseases PARP is a significant target for chemotherapeutic action. With 17 known members of the PARP family the mechanism of action for PARP’s activity is important to understand. The PARP protein consists of 4 important area’s; the Zinc figures where DNA repair takes place, a caspase cleavage function, a catalytic domain and a modification domain. Chemotherapeutic action is considered to be via the caspase domain or via the DNA repair domain. Inhibiting the repair of DNA strands triggers the automatic functions of cell death. Inhibitors for PARP have been developed and tested pre-clinically demonstrating the effectiveness of this approach. [Read the Full Post]

BELINOSTAT: THE UNUSUAL HDAC INHIBITOR

4622 | 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]

TOZASERTIB IN CLINICS FOR AURORA INHIBITION

5113 | Mar 13 2012

AURORA KINASE INHIBITION AND TOZASERTIB: Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). The initial results obtained for the Tozasertib Aurora kinase inhibitor has lead to its advancement into phase 1 and phase 2 clinical trials. [Read the Full Post]

Roles of sirtuins in the nervous system diseases

6608 | Nov 16 2011

As is reported in some studies, SIRT1 is expressed in the adult brain, with high levels in the cortex, hippocampus, cerebellum, and hypothalamus. In brain, SIRT2 is a cytoplasmic protein and plays an important role in the formation of myelin sheath and in the myelin-axon interaction. Other members of sirtuins is also found to exist in brain in various forms. Recent research indicates that a neuroprotective role of sirtuins, especially SIRT1 has been observed[1]. In fact, the effects of sirtuins on common neurological disorders has been described previously. [Read the Full Post]

Expression and activity of Sirtuins

5522 | Nov 15 2011

Sirtuins are a class of proteins that possess either histone deacetylase or mono-ribosyltransferase activity, and the activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Until now, seven members have been identified as sirtuin 1 (SIRT1) through SIRT 7. Of which, is considered to be one of the determining factors in longevity induced by calorie restriction. [Read the Full Post]

Roles of PIM serine/threonine kinases in cancers

6817 | Oct 27 2011

The Pim family of Ser/Thr kinases has been first identified in murine Moloney leukemia virus induced lymphomas, and is composed of three isoforms, Pim-1, Pim-2 and Pim-3. The following studies show that Pims are constitutively activated in many cancers. Of which, Pim-1 and Pim-2 were found to show the elevated levels mostly in hematologic malignancies and prostate cancer, while increased Pim-3 expression was mainly observed in different solid tumors. [Read the Full Post]

The combination of VE-465 and vincristine, the potential therapy for leukemia

7161 | Oct 25 2011

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells, and studies on the treatment of the disease have been carried out for many years. At present, a variety of small-molecule agents targeting specific leukemogenetic molecules have been used in preclinical or clinical treatment of leukemia. For example, BCR/ABL kinase inhibitors, including imatinib, nilotinib and dasatinib have shown the effective treatment against BCR/ABL-positive leukemia. However, novel agents and therapy may be still needed, since monotherapy shows only limited clinical efficacy. [Read the Full Post]

Enzastaurin, as the inhibitor of PKC, may be a novel PNC medical therapy

4559 | Sep 29 2011

Pancreatic cancer is the fourth most common cause of cancer death both in the United States. Regarding the pathology, pancreatic cancer mainly includes exocrine pancreas cancers, pancreatic cystic neoplasms and endocrine pancreatic cancers. Pancreatic neuroendocrine cancers (PNC) account for less than 3% of pancreatic tumors and the main treatments are surgery, hormone therapy, chemotherapy and so on at this stage. However, It is still needed to search for effective treatments for PNC, and understand the molecular pathways regulating neuroendocrine tumor cell proliferation. [Read the Full Post]

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

11599 | Sep 20 2011

Ovarian cancer is a cancerous growth arising from the ovary, and remains the leading cause of death from gynecological cancer, accounting for more than 140,000 deaths per year worldwide. The risk of developing ovarian cancer appears to be affected by several factors, and 10% of ovarian cancer patients have a family history of the disease. Certain genes defects (BRCA1 and BRCA2) are considered to be responsible for a small number of ovarian cancer cases. [Read the Full Post]

HDACs, play important roles in kidney development

5730 | 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]

Rosse, C., M. Linch, et al. (2010). "PKC and the control of localized signal dynamics." Nat Rev Mol Cell Biol 11(2): 103-112.

4663 | Jul 19 2011

This review which was published in Nature review summary the role of PKC in different pathways and show the importance of PKCs in controlling spatial resolution in signaling processes using the MET and STAT3 example. [Read the Full Post]

Mumenthaler, S. M., P. Y. Ng, et al. (2009). "Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes." Mol Cancer Ther 8(10): 2882-2893.

4766 | Jul 17 2011

These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. [Read the Full Post]

Chi V. Dang (2008)."The interplay between MYC and HIF in cancer" Nat Rev Cancer 8(1): 51-56

4344 | Jun 14 2011

This review concludes the interaction among MYC, HIF and cancer. It also concludes the cancer cellular responses in low oxygen levels. [Read the Full Post]

Takayuki Ikezoe (2008). “Aurora kinases as an anti-cancer target” Cancer Letters 262(2-3): 1–9

4235 | Jun 13 2011

This review highlights the function of Aurora kinases in the regulation of mitosis and presents the rationale for these kinases as an anti-cancer target. I also review recently developed inhibitors of Aurora kinases. [Read the Full Post]

Chen, L. S., S. Redkar, et al. (2009). "Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells." Blood 114(19): 4150-4157.

4432 | Jun 6 2011

Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. [Read the Full Post]

Mackay, H. J. and C. J. Twelves (2007). "Targeting the protein kinase C family: are we there yet?" Nat Rev Cancer 7(7): 554-562.

4286 | May 18 2011

This review summary the development of PKC inhibitors for cancer. It also explains the difficulties we meet. The author also give a prospect of PKC inhibitors. [Read the Full Post]

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

3525 | 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]

Bachmann, M. and T. Moroy (2005). "The serine/threonine kinase Pim-1." Int J Biochem Cell Biol 37(4): 726-730.

4594 | Apr 16 2011

Pim-1 is able to phosphorylate different targets, most of which are involved in cell cycle progression or apoptosis. Pim-1 expression can be induced by several external stimuli in particular by a number of cytokines relevant in the immune system, which led to the labeling of Pim-1 as a "booster" for the immune response. [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.

3583 | 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]

Semenza, G. L. (2003). "Targeting HIF-1 for cancer therapy." Nat Rev Cancer 3(10): 721-732.

5096 | Mar 19 2011

This article introduces the function of HIF-1, genes that are transcriptionally activated by HIF-1 and relationship between HIF-alpha and cancer. It also introduces HIF-1 targeted therapeutics. [Read the Full Post]

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Epigenetics

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

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