Olomorasib (LY3537982) is a highly selective and potent KRAS-G12C inhibitor, selectively inhibits growth of KRAS G12C mutant cells (IC50=1-60 nM).
LY3537982 does not inhibit growth of KRAS G12S/G13C/G12D mutant cells and WT KRAS cells (CI50>10 uM).
LY3537982 displays high selectivity for proteome-wide cysteine residues was evaluated using competitive chemical proteomics (8866 peptides).
LY3537982 inhibits the growth of subcutaneous EL3187 NSCLC PDX tumors in nude mice in a dose dependent manner.
LY3537982 demonstrates robust tumor regression in combination with other agents in KRAS G12C in vivo models.
LY3537982 is a promising KRAS G12C inhibitor predicted to deliver >90% KRAS G12C target occupancy in the clinic.
