Insilico nominates AI-designed VAV1 degrader ISM9546 for preclinical autoimmune disease development
Published in Artificial Intelligence, Drugs development & discovery, Immunology.
Publication date: October 13, 2026.
Insilico Medicine nominated ISM9546 as a preclinical candidate for autoimmune disease research. The oral molecular glue degrader targets VAV1, a protein involved in immune-cell signaling, with inflammatory bowel disease and rheumatoid arthritis among the proposed indications.
The company used its Chemistry42 platform to design and optimize candidates through repeated laboratory testing. ISM9546 is intended to act mainly outside the brain, with low central nervous system exposure.
According to Insilico, cell assays showed sub-nanomolar VAV1 degradation activity. In an animal model of acute colitis, the compound reduced disease-activity measures and improved histopathology scores by approximately 60%. The company also reports low brain exposure and short toxicity evaluations in rodents and non-human primates.
Limits: these are company-reported preclinical findings, without human efficacy or safety outcomes. The release does not provide detailed sample sizes or statistical analyses. Low brain exposure and 14-day toxicity testing do not establish long-term safety, including effects on infection risk or immune function. Candidate nomination is not clinical-trial clearance or drug approval.
Source: Insilico’s original release, October 13, 2026.