BMS-986466 (Bristol Myers Squibb)

BMS-986466 is an orally bioavailable small molecule inhibitor of Son of Sevenless homolog 1 (SOS1), developed by Bristol Myers Squibb. SOS1 is a guanine nucleotide exchange factor (GEF) that plays a critical role in the activation of RAS proteins by facilitating the exchange of GDP for GTP. By inhibiting SOS1, BMS-986466 prevents the reactivation of KRAS, thereby suppressing the hyperactivated MAPK signaling pathway that drives tumor growth in various cancers. It is currently being investigated in Phase 1/2 clinical trials, primarily in combination with KRAS G12C inhibitors such as adagrasib (with or without cetuximab), to treat advanced solid tumors harboring KRAS G12C mutations, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and biliary tract cancer (BTC).