Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects
760 views | Jun 30 2019
Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [Read the Full Post]
First-in-Human Phase I Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Antitumor Activity
362 views | Jun 30 2019
Gan HK et al. showed the tolerability profile of savolitinib was acceptable and the RP2D was established as 600 mg QD. Preliminary antitumor activity was demonstrated supporting further study in patients with PRCC. [Read the Full Post]
Design and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic
296 views | Jun 28 2019
Ramurthy S et al. indicated that a structure-based approach led to a pyridine series with an alcohol side chain that could interact with the DFG loop and significantly improved cell potency. Further mitigation of human intrinsic clearance and time-dependent inhibition led to the discovery of 15. Due to its excellent properties, it was progressed through toxicology studies and is being tested in phase 1 clinical trials. [Read the Full Post]
Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies
550 views | Jun 28 2019
Lang L et al. indicated their aim is to pinpoint the potential of FGFR4 as a therapeutic target and identify new avenues for advancing future research in the field. [Read the Full Post]
Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery
653 views | Jun 27 2019
Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]
Structural States of Hdm2 and HdmX: X-ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes
367 views | Jun 26 2019
Kallen J et al. used the same numbering for Hdm2 (as in Q00987) and HdmX (as in O15151, but minus 1). Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors. [Read the Full Post]
Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells
655 views | 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]
Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia
373 views | Jun 24 2019
Reyna DE et al. provides proof-of-concept for direct BAX activation as a treatment strategy in AML. [Read the Full Post]
Curaxin CBL0137 has the potential to reverse HIV-1 latency
549 views | Jun 24 2019
Jean MJ et al. indicated that CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach. [Read the Full Post]
Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells
825 views | 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]
Non-Photoinduced Biological Properties of Verteporfin
799 views | Jun 23 2019
Gibault F et al. showed that VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD. [Read the Full Post]
BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation
667 views | 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
654 views | 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]
TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response
844 views | Jun 21 2019
Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]
Raltegravir (MK-0518): an integrase inhibitor for the treatment of HIV-1
453 views | Jun 20 2019
Evering TH et al. indicated it has demonstrated a favorable side-effect profile in treatment-naive and -experienced patients and a subset of heavy treatment-experienced patients have been able a achieve virologic suppression with raltegravir as part of combination therapy despite limited treatment options. [Read the Full Post]
Efficacy of Ramelteon for delirium after lung cancer surgery
641 views | Jun 20 2019
Miyata R et al. showed that Ramelteon is likely to reduce the incidence and intensity of delirium after surgery for lung cancer in elderly patients. [Read the Full Post]
Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial
577 views | Jun 19 2019
Kimura K et al. showed that administration of 10 or 40mg/m2/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160mg/m2/day cohort. [Read the Full Post]
Histone deacetylase 6 inhibitor ACY-1215 protects against experimental acute liver failure by regulating the TLR4-MAPK/NF-κB pathway
2153 views | 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]
A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma
441 views | Jun 18 2019
Tang G et al. revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease. [Read the Full Post]
Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells
749 views | Jun 18 2019
Huang F et al. indicated the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. [Read the Full Post]