RMC-5127 (RMC5127) is a potent, selective and orally bioavailable RAS(ON) G12V inhibitor with EC50 of 2.1 nM, 26-fold selectivity over RAS WT.
RMC-5127 potently inhibits cellular pERK with IC50 of 0.6 nM in Capan-1 cell line.
RMC-5127 suppressed RAS pathway activity, inhibits cell proliferation, and induced apoptosis in a panel of KRASG12V mutant human cancer cells in vitro but only caused submaximal inhibition in the panel of K/N/HRAS wildtype cancer cells.
RMC-5127 (3-100 mg/kg po qd) induced profound and durable anti-tumor activity in subcutaneous CDX and PDX models of KRASG12V mutant NSCLC, PDAC, and CRC in vivo.
