RMC5127 is a first-in-class, orally bioavailable mutant-selective tri-complex inhibitor of the GTP-bound (ON) form of RASG12V. It non-covalently binds to cyclophilin A (CypA), forming a binary complex that engages RASG12V(ON) to form a high-affinity tri-complex, sterically inhibiting RAS binding. It inhibits the RAS pathway in KRASG12V-mutant cancer cells, reducing proliferation, inducing apoptosis, and showing strong potential for use in RASG12V-mutated cancer research.