ISM1354

ISM1354 is an AI-designed, next-generation small molecule GIPR (glucose-dependent insulinotropic polypeptide receptor) antagonist developed by Insilico Medicine. Nominated as a preclinical candidate (PCC) on September 30, 2026, ISM1354 is being developed for the treatment of obesity, obesity-related type 2 diabetes, and potentially cardiovascular diseases associated with obesity, such as obesity-associated heart failure. Developed using Insilico's proprietary generative AI platform, Chemistry42, ISM1354 was optimized to improve upon the company's earlier GIPR candidate, ISM0676, by offering enhanced pharmacokinetic and safety profiles. Preclinical studies demonstrated consistent oral bioavailability of 75–104% across multiple species (mice, rats, dogs, and monkeys) and at least an 18-fold greater plasma exposure compared to a clinical-stage benchmark compound. Additionally, ISM1354 showed weaker OATP1B1 inhibition and a wider hepatocyte safety margin, with no significant toxicity observed in a non-GLP monkey toxicology study.