FMC-242 + daraxonrasib

FMC-242 + daraxonrasib is an investigational combination of two targeted cancer therapies: FMC-242, a first-in-class, orally bioavailable, covalent allosteric breaker of the PI3Kα-RAS interaction developed by Frontier Medicines, and daraxonrasib (RMC-6236, Rasonque), an oral, non-covalent RAS(ON) multi-selective tri-complex inhibitor developed by Revolution Medicines. FMC-242 selectively binds to cysteine 242 in the RAS-binding domain of PI3Kα, disrupting its interaction with RAS and inhibiting downstream AKT signaling without affecting normal glucose homeostasis. Daraxonrasib binds to intracellular cyclophilin A to form a binary complex that selectively targets the active, GTP-bound state of multiple wild-type and mutant RAS isoforms (including KRAS, NRAS, and HRAS), blocking downstream MAPK signaling. In preclinical models, the combination of FMC-242 and daraxonrasib has demonstrated synergistic anti-tumor activity and robust tumor regression across multiple KRAS-mutant and RTK-driven solid tumor models, including those resistant to single-agent KRAS inhibitors.

Other names

FMC-242 + RMC-6236FMC-242 + RasonqueRMC-6236 + FMC-242Rasonque + FMC-242daraxonrasib + FMC-242