FMC-376

FMC-376 is an orally bioavailable, covalent small molecule inhibitor that selectively and irreversibly targets both the active (GTP-bound, "ON" state) and inactive (GDP-bound, "OFF" state) forms of the oncogenic KRAS G12C mutation. This dual mechanism of action is designed to overcome resistance and lack of response seen with earlier single-state KRAS G12C inhibitors. Preclinical studies have demonstrated that FMC-376 is highly effective in models resistant to first-generation inhibitors, showing robust anti-tumor activity across a broad panel of patient-derived xenograft models for non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer. The drug has also shown efficacy in intracranial NSCLC models with central nervous system metastasis. FMC-376 is being developed by Frontier Medicines Corporation as a potential best-in-class therapy for solid tumors harboring the KRAS G12C mutation.

Other names

KRAS G12C inhibitor FMC-376