The recently released WHO INN proposed names list includes the structure and name of Structure Therapeutics’ oral small molecule GLP-1R agonist, aleniglipron (GSBR-1290). Seemingly emerging from a “fast-follower” program based on Chugai/Eli Lilly’s orforglipron, the compound includes an unusual phosphine oxide motif and has shown positive results on plasma glucose levels and bodyweight in a Ph. IIa study ..read more

Pfizer disclosed the structure and discovery of their oral small molecule BDK inhibitor/degrader, PF-07328948, during the ACS Fall 2024 First-Time Disclosures session in Denver. The team identified a thiophene carboxylic acid-based hit targeting an allosteric pocket on BDK. Through optimization, they overcame challenges such as potential IADRs and BDK-E2 complex stabilization. By manipulating the dihedral angle of the methoxy group, they enhanced binding interactions, verifying PF-07328948's unexpected mechanism of action in vivo. PF-07328948 is currently Ph. I trials ..read more

Infection with the malaria parasite, Plasmodium falciparum, is a leading cause of fatality in the tropical regions of the world, with over 240M infections and >600k deaths each year. Currently, over half of the world population is at risk of infection and with the rise of resistance against current treatments, the need for new antimalarials is clear. At the ACS Fall 2024 conference in Denver, CO, Novartis outlined the structure and discovery story of NVP-IWY357, a novel antimalarial that has no cross-resistance to current drugs and the potential to achieve a single-dose cure ..read more

August’s Molecules of the Month include Kannalife Sciences’ GPR55 antagonist for chemotherapy-induced neuropathic pain and Boehringer Ingelheim’s zwitterionic inhibitor of KHK for metabolic disorders. We also feature bomedemstat, Merck’s irreversible LSD1 inhibitor, which has entered a pivotal Ph. III trial. Other notable molecules from August include a small peptide inhibitor of the Fas receptor from ONL Therapeutics and Boehringer Ingelheim’s PDE4B inhibitor with the potential to treat IPF. You can read more about the compounds that made our August 2024 Molecules of the Month list and check ..read more

ONL1204 is ONL Therapeutics small peptide inhibitor of the Fas receptor for IRD ..read more

Vactosertib is an orally bioavailable TGFβ type I receptor kinase inhibitor, that has demonstrated safety, tolerability, and clinical efficacy in combination with pomalidomide in a Ph. Ib trial for RRMM ..read more

Nerandomilast (BI 1015550) is Boehringer Ingelheim’s PDE4B inhibitor with demonstrated clinical potential in treating IPF ..read more

Xanamem is Actinogen Medical's cortisol-blocking drug targeting the 11β-HSD1 (11β-hydroxysteroid dehydrogenase) enzyme ..read more

BAY-2925976 is a highly selective ARα2C (alpha-2c adrenergic receptor) antagonist with improved brain penetration and efficacy, aimed at treating OSA ..read more

Bomedemstat (MK-3543, IMG-7289) is Merck’s irreversible LSD1 (lysine-specific demethylase 1) inhibitor for MPNs ..read more