RMC-4998 

RMC-4998 is an orally active inhibitor targeting the active or GTP-bound state of the KRAS^G12C mutant. RMC-4998 can form a ternary complex with intracellular CYPA and the activated KRAS^G12C mutant, with an IC₅₀ value of 28 nM. RMC-4998 can inhibit ERK signaling in KRAS^G12C mutant cancer cells and induce apoptosis. RMC-4998 can be used for tumor research^[1][2].

KRAS^G12C[1].

RMC-4998 (100 nM, 120 h) disrupts oncogenic signaling in KRAS^G12C mutant cells by recruiting cyclophilin A (CYPA) to the active state of mutant KRAS^[1].
RMC-4998 can inhibit the expression of ERK signaling related proteins and cell proliferation in KRAS^G12C mutant cancer cells^[1].
RMC-4998 (0-1000 nM, 72 h) inhibits lung cancer cell viability by suppressing the PI3K/mTOR and ERK signaling pathways^[2].
RMC-4998 (30 nM, 96 h) can inhibit ERK protein phosphorylation and suppress LU65 cell viability^[3].

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

RMC-4998 (10-200 mg/kg; once daily; 28 days; p.o.) inhibits ERK phosphorylation in tumors and exhibits anti-tumor activity in mice carrying NCI-H358 xenografts^[1].
RMC-4998 (80 mg/kg; once daily; 4 weeks; p.o.) can promote tumor regression in non-small cell lung cancer mice and has anti-tumor activity^[2].
RMC-4998 (100 mg/kg; once daily; p.o.) induces tumor regression and inhibits ERK phosphorylation expression in sotorasib-R LU65 xenograft mice^[3].

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

983.25

C₅₇H₇₄N₈O₇

2642037-07-6

Solid

White to off-white

O=C(N1CCC[C@@H](C2=O)N1)[C@@H](NC([C@H](C(C)C)N3C([C@@]4(CCN(C(C#CC(C)(C)N(C)C)=O)C4)CC3)=O)=O)CC5=CC(C6=CC(C(CC(C)(C)CO2)=[C@@]([C@@]7=C([C@H](C)OC)N=CC=C7)N8CC)=C8C=C6)=CC=C5

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [1]. Schulze CJ, et al. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799.  [Content Brief]

  [2]. Kitai H,et al. Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer. Nat Commun. 2024 Jul 19;15(1):6076.  [Content Brief]

  [3]. Solanki H S, et al. RTK signaling and WT RAS activity as vulnerabilities in tumors with acquired resistance to GDP-state selective KRASG12C inhibitors in preclinical models[J]. Cancer Research, 2024, 84(6_Supplement): 1924-1924.