Insilico Medicine Unveils AI-Designed GIPR Antagonist for Obesity

The company’s proprietary Chemistry42 platform enabled the development of ISM1354 by optimizing molecular interactions and filtering for potential toxicity early in the design phase. Preclinical results across multiple species, including mice, rats, and monkeys, showed oral bioavailability between 75% and 104%. Notably, the compound demonstrated an 18-fold increase in plasma exposure compared to a clinical-stage benchmark, alongside a significantly wider hepatocyte safety margin.

Feng Ren, Co-CEO and CSO of Insilico Medicine, noted that the structural complexity of GIPR receptors typically hinders small-molecule discovery. By using AI to balance potency and safety, the team bypassed the toxicity hurdles that have stalled other candidates in the GLP-1 and GIPR space. In non-GLP toxicology assessments, ISM1354 showed no significant adverse findings and an estimated 45-fold margin of safety.

This nomination marks the tenth preclinical candidate Insilico has produced in 2026, contributing to a total of 34 candidates since 2021. The firm reported a profitable first half of 2026, with revenue reaching approximately $106 million, supported by high-value collaborations with major pharmaceutical players. As obesity treatments evolve toward longevity-focused therapies, Insilico is positioning its AI-driven pipeline to provide alternatives that avoid the physical decline often associated with rapid weight loss.