RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (K d = 195 nM) and KRAS (G12V) (K d = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK , CRAF , and RSK , as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRAS G12C cancer models, and demonstrates good tolerability across various RAS cancer models.