RM-018 is a powerful tricomplex inhibitor that specifically targets the active state of KRAS G12C. It exhibits unique functional characteristics and possesses the ability to bind and inhibit both KRAS G12C and KRAS G12C/Y96D, potentially overcoming resistance.

RM-018 is classified as a "tricomplex" KRAS inhibitor that strategically utilizes cyclophilin A, a prevalent chaperone protein, to specifically target and inhibit KRAS G12C[1]. At concentrations ranging from 0.01 to 1000 nM over a 72-hour period, RM-018 demonstrates IC50 values between 1.4-3.5 nM for KRAS G12C and 2.8-7.3 nM for KRAS G12C/Y96D across various cell lines, including NCI-H358, MIA PaCa-2, Ba/F3, and MGH1138-1[1]. Furthermore, a 4-hour exposure to RM-018 at 0-100 nM significantly downregulates KRAS, pERK, and pRSK protein expression[1]. In cell viability assays, RM-018, administered at 0.01-1000 nM for 72 hours, effectively inhibited cellular activity in NCI-H358, MIA PaCa-2, Ba/F3, and MGH1138-1 cells with stable KRAS G12C or KRAS G12C/Y96D expression, with minimal effect from KRAS G12C/Y96D expression itself[1]. Western blot analysis further confirmed that RM-018 suppresses KRAS, pERK, and pRSK protein levels in MIA PaCa-2, HEK293T, and MGH1138-1 cells expressing KRAS G12C or KRAS G12C/Y96D, when treated with 0-100 nM for 4 hours, showing similar efficacy across evaluations[1].