Category
- PI3K/Akt/mTOR
- Epigenetics
- Methylation
- Immunology & Inflammation
- Protein Tyrosine Kinase
- Angiogenesis
- Apoptosis
- Autophagy
- ER stress & UPR
- JAK/STAT
- MAPK
- Cytoskeletal Signaling
- Cell Cycle
- TGF-beta/Smad
- DNA Damage
- Stem Cells & Wnt
- Ubiquitin
- Neuronal Signaling
- NF-κB
- GPCR & G Protein
- Endocrinology & Hormones
- Transmembrane Transporters
- Metabolism
- Proteases
- Microbiology
- Others
Archives
Epigenetics
PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
2 | 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
1 | 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
2 | 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
1 | 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
13 | 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
10 | 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
18 | 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
18 | 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
17 | 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
22 | 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
32 | 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]
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
27 | 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
51 | 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
36 | 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
20 | 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
44 | 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
67 | 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
82 | 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]
Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma
70 | 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
64 | 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
60 | 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
103 | 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
125 | 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
103 | 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
132 | 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
115 | 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
111 | 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
205 | 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
141 | 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
130 | 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
108 | 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
92 | 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
152 | 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
148 | 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
140 | 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
81 | 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
272 | 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
91 | 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
88 | 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
86 | 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]
PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation
113 | 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.
96 | 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
179 | 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
103 | Aug 07 2019
Liu Y et al. demonstrated that autophagy played a cyto-protective role in talazoparib-treated pediatric CML and co-treatment with talazoparib and autophagy inhibitor could induce synergetic anti-tumor effect, providing novel insights for pediatric CML treatment. [Read the Full Post]
Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression
0 | Jul 27 2019
Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]
JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma
56 | 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
104 | 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
78 | 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
271 | 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)
98 | 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
160 | 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
112 | 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
106 | 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
152 | 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
122 | 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
123 | 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
404 | 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]
Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin
145 | 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)
132 | 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]
Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition
140 | 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
99 | 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
186 | May 09 2019
Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]
Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo
164 | May 07 2019
Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]
Thromboembolic events in polycythemia vera
306 | 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
340 | 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
639 | 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
199 | 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
247 | 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
153 | 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
202 | 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
211 | 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
182 | 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
216 | Mar 28 2019
Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]
The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat
181 | 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
185 | 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
246 | 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
135 | Mar 11 2019
Wang YM et al. suggested that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment. [Read the Full Post]
Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN
253 | 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]
Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts
206 | 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]
Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival
206 | 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
147 | 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
154 | 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
201 | Feb 18 2019
Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]
PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia
134 | 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
257 | 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
856 | 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
333 | 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
649 | 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
287 | 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
277 | 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
268 | 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
565 | 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
457 | 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
496 | 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
183 | 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
366 | 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
270 | 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
339 | 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
589 | 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]
PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage
794 | 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]
SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells
558 | 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
2499 | 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
782 | 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
812 | 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
359 | 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
576 | 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
688 | 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
457 | 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
711 | 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
402 | 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
777 | 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
416 | 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.
381 | 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
244 | 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
563 | 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
511 | 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
749 | 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]
Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis
940 | 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
465 | 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
701 | Aug 05 2018
Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]
AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition
922 | 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
657 | 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
1964 | 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
637 | 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]
Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways
539 | 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
483 | 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
480 | 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
652 | 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
598 | 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
947 | 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
1544 | 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
2143 | 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
360 | 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
611 | 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
639 | 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
704 | 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
600 | 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
812 | 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
713 | 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
967 | 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
1712 | 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
1166 | 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
351 | 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]
Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells
0 | May 21 2018
Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]
Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway
0 | May 12 2018
Yun T et al. found that HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]
A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta
1056 | 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
547 | 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
1064 | 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
545 | 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
2152 | 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
767 | 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
964 | 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]
Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation
987 | 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
1276 | 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]
NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells
1064 | 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
984 | 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
662 | 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
1112 | 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]
Reprogramming of histone methylation controls the differentiation of monocytes into macrophages
465 | 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]
Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis
1860 | 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
472 | 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
460 | 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
1362 | 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
843 | 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]
Concomitant BET and MAPK blockade for effective treatment of ovarian cancer
542 | 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
2502 | 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
1065 | 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
817 | 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
1287 | 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
1305 | 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
994 | 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
867 | 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
952 | 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
629 | 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
595 | 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
1334 | 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]
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma
1653 | 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
560 | 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
872 | 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
1182 | 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
1167 | 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
3022 | 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
955 | 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.
1241 | 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
589 | 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
874 | 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
722 | 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
1407 | 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
1397 | 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
1490 | 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
1632 | 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]
EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer
626 | 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
1262 | 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
1096 | 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
1594 | 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
1744 | 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
1968 | 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.
1737 | 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
4836 | 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
1647 | 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
2743 | Jun 11 2017
Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]
Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells
1436 | 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
1529 | 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
1633 | 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
2346 | 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
2128 | May 17 2017
Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]
Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells
0 | May 12 2017
Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]
Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.
0 | May 10 2017
Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]
Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.
0 | May 10 2017
Those results improve Li Det al.'s understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]
Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.
0 | May 09 2017
Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]
Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways
1518 | 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
2737 | 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
1465 | 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
1204 | 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
2118 | 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
1321 | 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]
HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells
2768 | 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
1414 | 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
860 | 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]
Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice
2596 | 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
2201 | 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]
Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death
1572 | 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
1640 | 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]
NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2
1133 | 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]
The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
1976 | 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
2326 | 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
1812 | 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
2222 | 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
3206 | 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
2335 | 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
1728 | Nov 23 2016
Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]
Nucleoside Inhibitors of Zika Virus
1073 | 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
1692 | 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
1704 | 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.
2236 | 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
1863 | 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
2288 | Oct 31 2016
Shinde V, et al. found that the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. [Read the Full Post]
Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1
4523 | Oct 27 2016
Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]
Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3'-monoxime
2000 | Oct 21 2016
Heiss EH et al. demonstrated that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. [Read the Full Post]
Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ
2398 | Oct 20 2016
Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]
Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3
2508 | Oct 09 2016
Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]
Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer
2257 | 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
2222 | 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
1058 | 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
1889 | 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
3607 | 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
4287 | 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
4484 | 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
8333 | 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
4368 | 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
3572 | 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
5434 | 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]
Recently identified CHEK2 Y390C mutation facilitates early breast cancer development
5845 | 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
4311 | 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
4225 | 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
4502 | 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
5771 | 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
5945 | 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
10361 | 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
4608 | 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
4308 | 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
7444 | 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
2705 | 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
6127 | 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
7582 | 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
3884 | 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
9384 | 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]
Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion
7654 | 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
4889 | 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
6249 | 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
4873 | 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
3774 | 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
3701 | 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
3670 | 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
3818 | 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
3796 | 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
3694 | 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
5828 | 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
3704 | 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
4119 | 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
3371 | 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
3536 | 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
3913 | 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
3817 | 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
3637 | 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
3238 | 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
3591 | 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
6460 | 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
4228 | 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
3402 | 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]
MS275 strongly inhibits HDAC1 and HDAC3 with IC50
3346 | 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
3286 | 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
3086 | 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
3545 | 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
4070 | Apr 16 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]
Vorinostat is a member of a larger class of compounds that inhibit histone deacetylases
3441 | 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]
Activation of the HIF pathway in cancer
4147 | 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]
HDAC is also shown to occur in an inhibitor
3791 | 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
3752 | 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
4267 | 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
3156 | 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
3897 | 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
4141 | 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
3942 | 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
3747 | 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
3407 | 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
3461 | 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
3081 | 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
3198 | 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
4045 | 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
3832 | 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
3466 | 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
2794 | 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
3330 | 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
3278 | 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
3056 | Apr 16 2012
EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. Various assays for HDACs have been developed that are used for the analysis of HDAC levels. [Read the Full Post]
OLAPARIB: THE FIRST PARP INHIBITOR
4394 | 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
4834 | 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
3548 | 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
3304 | 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
3504 | 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
6153 | 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]
INCB18424 – JACKING THE JAK2
6831 | 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
2811 | 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
5085 | 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
6499 | 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
3077 | 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
3860 | 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
5163 | 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
6599 | 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
3714 | 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
4368 | 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
4929 | 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
6333 | 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
5264 | 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
6578 | 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
6928 | 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]
Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer
11363 | 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
5531 | 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]
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.
4551 | 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
4198 | 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
4121 | 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.
4260 | 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]
Ekwall, K. (2005). "Genome-wide analysis of HDAC function." Trends Genet 21(11): 608-615.
3366 | 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.
4402 | 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.
3395 | 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.
4970 | 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]
