ISM8001

ISM8001 is a novel, covalent, and selective dual inhibitor of fibroblast growth factor receptors 2 and 3 (FGFR2 and FGFR3), developed by Insilico Medicine. It was designed to address the limitations of first-generation pan-FGFR inhibitors, specifically off-isoform toxicities such as FGFR1-mediated hyperphosphatemia and FGFR4-mediated diarrhea, as well as acquired resistance mutations in the FGFR2/3 kinase domains. Preclinically, ISM8001 has demonstrated high selectivity for FGFR2 and FGFR3 over FGFR1 and FGFR4, and potent activity against various FGFR2/3 aberrations, including gatekeeper mutations like FGFR2-V564F and FGFR3-V555M. The compound is classified as a BCS II molecule with favorable oral bioavailability and has shown robust anti-tumor efficacy in xenograft models of gastric, endometrial, and bladder cancers.