RMC-7977 is broad spectrum inhibitor of both mutant and wild-type KRAS, NRAS, and HRAS variants.1 It binds with high affinity to cyclophilin A (KD = 195 nM) creating a binary complex that has high affinity for the active state of KRAS (KD = 85 nM for G12V). Active in in vivo xenograft models of NSCLC, CRC, and PDAC.1,2,3 RMC-7977 was able to overcome resistance to the KRASG12D selective inhibitor MRTX1133.1
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