Chemistry:Daraxonrasib

Daraxonrasib (RMC-6236) is a RAS inhibitor drug. It is undergoing testing by Revolution Medicines to treat advanced solid tumors with RAS mutations, especially metastatic pancreatic ductal adenocarcinoma (PDAC) containing KRAS G12X mutations. It received a breakthrough therapy designation from the US FDA in 2025.

Daraxonrasib is an orally active and multi-selective RAS inhibitor. It uses a tri-complex mechanism to target the active, GTP-bound form of RAS proteins, including mutant and wild-type forms. Unlike conventional RAS inhibitors, it first binds to the chaperone-like protein cyclophilin A to form a complex, which then attaches to active RAS. This interaction blocks downstream effector binding and inhibits oncogenic signaling.

In 2026, daraxonrasib completed a phase 3 clinical trial (RASolute 302) to assess efficacy compared to standard-of-care chemotherapy. The trial met all primary and key secondary endpoints, including progression-free survival (PFS). The company reported median survival of 13.2 months with daraxonrasib vs. 6.7 months with standard chemotherapy. The hazard ratio for death was 0.40 (a 60% reduction in risk of death; p < 0.0001). Daraxonrasib was generally well tolerated with a manageable safety profile and no new safety signals. Although the trial was randomized, it was open-label (not blinded), and both the patient and outcome assessors knew if a patient was administered Daraxonrasib.

See also

• Ras GTPase
• Pancreatic cancer