RMC-6236 is broad spectrum inhibitor of both mutant and wild-type KRAS, NRAS, and HRAS variants.1,2 It binds with high affinity to cyclophilin A (KD = 55 nM) creating a binary complex that has high affinity for the active state of KRAS (KD = 131 nM for G12V, 364 nM for G12D and 154 nM for wild type). Active in in vivo xenograft models of NSCLC, PDAC, colorectal cancer, gastric carcinoma, and ovarian adenocarcinoma.2
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