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TNG462, developed by Tango Therapeutics, is a potential best-in-class, oral, protein arginine methyltransferase 5 (PRMT5) inhibitor currently in Ph. I/II clinical trial for MTAP-deleted solid tumors. TNG462 is designed to cooperatively bind to PRMT5 when complexed with its endogenous inhibitor methylthioadenosine (MTA), which accumulates in MTAP-deleted tumors. This triggers synthetic lethality in cells with an MTAP-deletion and spares healthy tissues with low MTA levels. A CNS-permeable analogue, TNG908, is also entering clinical trials for MTAP-deleted glioblastoma.
VVD-214/RO7589831 is an oral covalent, reversible, and allosteric inhibitor of WRN helicase discovered by the San Diego-based biotech Vividion Therapeutics and being developed by Roche for tumors marked by microsatellite instability and/or mismatch repair deficiency. Vividion has utilized its chemoproteomics platform to discover and develop novel treatment options for oncology targets. The structure and initial preclinical pharmacology data for VVD-214 were recently disclosed at the AACR Annual Meeting 2024 in San Diego. VVD-214 is currently being evaluated in a Ph. I trial.
Peptidic GLP-1R agonists have received significant media coverage over the past year for their astounding efficacy in several indications. While most of the recent fanfare has been related to their role in weight loss, GLP-1R agonists have been a mainstay of the type 2 diabetes treatment landscape for the past 2 decades. GLP-1R agonists have also recently shown efficacy in reducing heart disease risk and treating certain chronic kidney diseases. Here’s a recap of the March 14th, 2024, Flash Talk, from Oliver Philps.
If you are as excited as we are about this new era of non-opioid pain management and want to learn more, explore our series of articles that unravel the fascinating history of target validation of voltage-gated sodium channels, showcase the breakthroughs achieved so far, and look forward to what lies ahead for the industry.
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