Definition

An orally bioavailable, covalent inhibitor of the active, guanosine triphosphate (GTP)-bound form of the oncogenic KRAS substitution mutation G12C, KRAS G12C(ON), with potential antineoplastic activity. Upon oral administration, KRAS G12C inhibitor RMC-6291 forms a tri-complex with the intracellular chaperone protein and immunophilin cyclophilin A (CypA) and KRAS G12C(ON). This tri-complex inhibits KRAS G12C(ON)-mediated signaling, which may inhibit tumor cell proliferation. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.