RMC-6236 is a potent RAS(ON)MULTI inhibitor with broad-spectrum inhibitory activity against RAS-GTP and can be used in cancer research.

METHODS: HPAC and Capan-2 cell lines were treated with RMC-6236 (1, 3, 10, 30 nM, 4 hours) and Western Blot analysis was performed.
RESULTS Time- and concentration-dependent inhibition of RAS pathway signaling markers pERK, pAKT, and pS6 were observed in HPAC and Capan-2 cell lines treated with RMC-6236. The inhibition of pERK and pS6 in Capan-2 cells lasted for at least 48 hours. HPAC cells also showed sustained pERK inhibition and time-dependent induction of apoptosis. [2]

METHODS: RMC-6236 (3, 10, 25 mg/kg, oral) was administered to mice bearing Capan-2 xenograft tumors. The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of RMC-6236 as well as its antitumor activity in vivo in a range of mutant RAS-driven human tumor xenograft models were evaluated.
RESULTS RMC-6236 exhibited similar PK profiles in multiple xenograft models and did not accumulate in the blood and tumors after repeated dosing; RMC-6236 exposure in various xenograft tumors was approximately 3 to 7 times higher than that in the blood and was cleared relatively slowly from the tumors; consistent with the dose-dependent and prolonged exposure in xenograft tumors, oral administration of RMC-6236 resulted in dose-dependent and persistent inhibition of RAS pathway signaling. [2]