RM-018 is a potent, functionally distinct tricomplex KRAS G12C active-state inhibitor. RM-018 retains the ability to bind and inhibit KRAS G12C/Y96D and could overcome resistance. RM-018 binds specifically to the GTP-bound, active [“RAS(ON)”] state of KRAS G12C In Vitro RM-018 is a “tricomplex” KRAS inhibitor, which exploits a highly abundant chaperone protein, cyclophilin A, to bind and inhibit KRAS G12C. ?\nRM-018 (0.01-1000 nM; 72 hours) has IC 50 s of 1.4-3.5 nM (KRAS G12C ) and 2.8-7.3 nM (KRAS G12C/Y96D ) in NCI-H358, MIA PaCa-2, Ba/F3, and MGH1138-1 cells. ?\nRM-018 (0-100 nM; 4 hours) inhibits the expression of KRAS, pERK, and pRSK protein. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: NCI-H358, MIA PaCa-2, Ba/F3, and MGH1138-1 cells, which stably infected with KRAS G12C or KRAS G12C/Y96D . Concentration: 0.01-1000 nM Incubation Time: 72 hours Result: Inhibited the cell activity, but largely unaffected by KRAS G12C/Y96D expression. Western Blot AnalysisCell Line: MIA PaCa-2, HEK293T and MGH1138-1 cells, which expressing KRAS G12C or KRAS G12C/Y96D . Concentration: 0-100 nM Incubation Time: 4 hours Result: Inhibited KRAS, pERK and pRSK levels with similar potency. Form:Solid IC50& Target:KRAS (G12C) KRAS (G12C/Y96D)