Daraxonrasib (RMC-6236)6 is an orally effective and novel triple complex RAS (ON) MULTI inhibitor, which is a potent non covalent inhibitor of multiple RAS variants in GTP binding state. RMC-6236 has anti-tumor activity and can be used in research related to RAS driven tumors. With rich experience in compound synthesis, we can provide fast customized synthesis services for this product according to your research needs.

KRAS (WT):154 nM (KD2), KRAS (G12V):131 nM (KD2), CYPA:55.3 nM (KD1), KRas (G12D):364 nM (KD2)

METHODS: HPAC and Capan-2 cell lines were treated with Daraxonrasib (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 Daraxonrasib (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. [1]

METHODS: Daraxonrasib (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.
RESULTSDaraxonrasib (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. [1]