FS-207

FS-207 is a potent and selective small-molecule inhibitor of the Werner Syndrome RecQ helicase (WRN), developed by Foresight Therapeutics for the treatment of microsatellite instability-high (MSI-H) cancers. MSI-H tumors, which have impaired DNA mismatch repair, exhibit a synthetic lethal dependency on WRN helicase. FS-207 inhibits WRN helicase and ATPase activity with low nanomolar potency and demonstrates over 1000-fold selectivity over other RecQ helicases. By inhibiting WRN, the drug induces chromosomal structural aberrations and triggers the DNA damage response pathway, selectively killing MSI-H cancer cells. Preclinical studies have shown robust tumor regression in cell line-derived (CDX) and patient-derived (PDX) xenograft models with favorable oral bioavailability and tolerability. FS-207 is expected to enter clinical trials in 2026.