RMC-4998 TFA is an orally active inhibitor targeting the active or GTP-bound state of the KRAS G12C mutant. RMC-4998 TFA can form a ternary complex with intracellular CYPA and the activated KRAS G12C mutant, with an IC50 value of 28 nM. RMC-4998 TFA can inhibit ERK signaling in KRAS G12C mutant cancer cells and induce apoptosis. RMC-4998 TFA can be used for for non-small cell lung cancer (NSCLC) research [1] [2] [3].
References:
[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.
[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.
[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.
References:
[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.
[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.
[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.