RM-041 

RM-041 is a selective, orally active KRAS^G13C (ON) inhibitor that forms a covalent complex with KRAS^G13C (ON) and Cyclophilin A. RM-041 blocks the binding of RAS effector proteins via steric hindrance, and then covalently binds to Cys-13 to form an irreversible inhibitory complex, thereby inhibiting the proliferation of KRAS^G13C mutant cancer cells. RM-041 induces regression of KRAS^G13C tumors in cellular and xenograft tumor models. RM-041 exerts a synergistic effect when combined with upstream node inhibitors (such as SHP2 inhibitors). RM-041 can be used for the research of non-small cell lung cancer^[1].

Compared with KRAS^G12C, KRAS^G13C exhibits a higher spontaneous nucleotide exchange rate, which reduces its dependence on guanine nucleotide exchange factor (GEF) reloading and its sensitivity to upstream inhibitors such as SHP2 and SOS1. Therefore, therapies targeting KRAS^G13C mutant tumors need to directly inhibit KRAS^G13C. In addition, KRAS^G13C shows unique sensitivity to specific GTPase-activating proteins (GAP), including NF1^[1].
Preclinical Combination Therapy Strategy:
RM-041 is used to specifically inhibit mutant KRAS^G13C, while combined with targeted inhibition of key upstream nodes such as SHP2 to attenuate the synergistic effects mediated by wild-type RAS signaling^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Oral administration of RM-041 leads to profound and sustained inhibition of RAS pathway activity in KRAS^G13C xenograft tumor models, and induces in vivo tumor regression at tolerated doses^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1032.20

C₅₄H₇₂F₃N₉O₈

2953276-07-6

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Schulze C J, et al. a first-in-class tri-complex KRASG13C (ON) inhibitor validates therapeutic targeting of KRASG13Cand drives tumor regressions in preclinical models[J]. Cancer Research, 2022, 82(12_Supplement): 3598-3598.