An Allosteric Pan-Mutant-Selective PI3Kα Inhibitor Without Hyperglycemia in Preclinical Models
RLY-2608
oral allosteric pan-mutant isoform-selective PI3Kα inhibitor Ph. I for PIK3CA mutant cancers from DEL screen for mutant-specific allosteric inhibitors Cancer Discov., November 2023 D.E. Shaw Research / Relay Therapeutics
Other molecules you may be interested in
NT-0796
NT-0796 is NodThera's pro-drug inhibitor of the NLRP3 inflammasome. NT-0796 is currently in a Ph. Ib/IIa trial in obese individuals at risk of developing atherosclerotic cardiovascular diseases. NT-0796 has the potential to reduce neuroinflammation in Parkinson’s disease. The NLRP3 inflammasome has emerged as a hot target due to its connection to Alzheimer’s disease, Parkinson’s disease, gout, and other diseases. Here is a detailed review of the role of NLRP3 inhibition in treating atherosclerosis, how NT-0796 was identified, and what makes it special, clinical development, and more.
gridegalutamide (BMS-986365, CC-94676)
BMS-986365 is a potential best-in-class heterobifunctional ligand-directed degrader of WT AR. This full case study details how this heterobifunctional degrader was engineered to have low intrinsic agonism and exert direct antagonism of WT AR through occupancy of its ligand-binding domain, how the dual modality of BMS-986365 results in deep AR pathway inhibition and allows antagonism to reinforce degradation to combat compensatory resistance mechanisms, its attractive preclinical profile, interim clinical data, how it differentiates from Arvinas’ first-to-clinic AR degraders, and more!
AZD0780
AstraZeneca recently disclosed the structure and discovery journey of their oral small molecule PCSK9 inhibitor, AZD0780, during the ACS Fall 2024 First Time Disclosures session in Denver. Discover how the team identified a fragment hit targeting a previously unexplored pocket, verified its novel mechanism of action, and successfully advanced it into a clinical compound now in Ph. II trials for patients with dyslipidemia.
casdatifan (AB521)
Arcus Biosciences recently disclosed the structure and discovery story of their oral HIF-2α inhibitor casdatifan (AB521) at the ACS Fall 2024 First Time Disclosures session in Denver. Read on to find out how the team overcame serum shifts and metabolism issues to deliver into the clinic what could potentially be a best-in-class compound, superior to the recently approved inhibitor, belzutifan.
bomedemstat (MK-3543, IMG-7289)
Bomedemstat (MK-3543, IMG-7289) is Merck’s irreversible LSD1 (lysine-specific demethylase 1) inhibitor for MPNs.
