RMC-5127

RMC-5127 is a first-in-class, orally bioavailable, mutant-selective tri-complex inhibitor that targets the GTP-bound (active/ON) form of KRASG12V. It is designed to selectively inhibit the oncogenic KRASG12V mutation found in various cancers, while sparing wild-type K/N/HRAS. The drug works by binding with high affinity to cyclophilin A (CypA), creating a neomorphic interface that enables selective inhibition of KRASG12V-driven signaling and tumor cell proliferation. Preclinical studies have shown that RMC-5127 induces deep suppression of the RAS pathway, inhibits cell proliferation, and induces apoptosis in KRASG12V-mutant cancer cells. It has demonstrated CNS penetration and durable anti-tumor activity in both subcutaneous and intracranial xenograft models. Developed by Revolution Medicines, it is being investigated for use in advanced solid tumors harboring KRAS G12V mutations[1][2][3][5].