pf-07985045

PF-07985045 is an investigational small molecule inhibitor developed by Pfizer that targets KRAS, a GTPase protein frequently mutated in human solid tumors. It is described as a panKRAS "ON/OFF" inhibitor, meaning it binds to both the active (GTP-bound) and inactive (GDP-bound) states of wild-type and mutant KRAS isoforms. Preclinical studies show that PF-07985045 has high selectivity for KRAS over other RAS family members (HRAS, NRAS), with more than 2000-fold selectivity. The drug blocks the binding of RAF-RBD to GTP-loaded KRAS mutants, thereby inhibiting downstream signaling pathways involved in tumor growth and survival. It has demonstrated anti-tumor efficacy in xenograft models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Currently, it is being evaluated in Phase 1 clinical trials as monotherapy or in combination with other anti-cancer agents for advanced solid tumors including pancreatic ductal carcinoma, colorectal cancer, and non-small cell lung cancer[4][5][7][9].