Insilico Medicine has nominated ISM1354, an AI-driven small molecule preclinical candidate targeting the glucose-dependent insulinotropic polypeptide receptor for potential intervention in obesity, type 2 diabetes and related cardiometabolic conditions.
The company claims preclinical evaluation showed oral bioavailability of 75-104% across mice, rats, dogs and monkeys and at the same dose produced at least 18-fold greater plasma exposure than a clinical-stage benchmark.
Insilico claims safety findings include substantially weaker inhibition of the hepatic transporter OATP1B1 versus the benchmark, minimal hepatocyte cytotoxicity at concentrations up to 200 μM compared with benchmark IC50 values of about 25 μM in human hepatocytes and about 20 μM in monkey hepatocytes, and an estimated 45-fold margin of safety in a non-GLP monkey toxicology assessment.
The nomination followed multi-objective AI-driven molecular generation and optimization using its Chemistry42 platform with DILI screening, free energy perturbation and iterative design-make-test-analyze cycles, and the data support progression to GLP toxicology studies and further development discussions.
Insilico also reports it nominated 10 preclinical candidate compounds in the first nine months of 2026, bringing total PCC nominations since 2021 to 34.
