Definition

An orally bioavailable inhibitor of the active, guanosine triphosphate (GTP)-bound form of both wild type and mutant variants of the RAS isoforms, including HRAS, NRAS and KRAS, with potential antineoplastic activity. Upon oral administration, RAS inhibitor RMC-6236 binds to an intracellular chaperone protein, cyclophilin A (CypA). The resulting inhibitory binary complex binds to active, GTP-bound RAS to form a tri-complex. This tri-complex inhibits RAS-dependent signaling and inhibits the proliferation of tumor cells in which RAS is overexpressed and/or mutated. RAS plays an important role in cell signaling, division and differentiation. Mutations of RAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.