RMC-4998 (RM-029) | KRAS G12C inhibitor

Chemical Structure : RMC-4998

CAS No.: 2642037-07-6

RMC-4998 (RMC4998, RM-029)

Catalog No.: PC-21063Not For Human Use, Lab Use Only.

RMC-4998 (RM-029) is a tricomplex inhibitor that targets the active state or GTP-bound state of KRAS G12C, selectively inhibits the proliferation of KRASG12C mutant cells with mean IC50 of 0.28 nM.

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Biological Activity

RMC-4998 (RM-029) is a tricomplex inhibitor that targets the active state or GTP-bound state of KRAS G12C, selectively inhibits the proliferation of KRASG12C mutant cells with mean IC50 of 0.28 nM.
RMC-4998 exhibits greater binding affinity (inhibition constant (KI): 272,000 M−1 s−1 (kinact/KI): 272,000 M−1s−1]) than that of existing inactive state-selective inhibitors.
RMC-4998 induces a tricomplex between KRASG12C and CYPA in live cells without affecting wild-type KRAS, NRAS, or HRAS.
RMC-4998 shows comparable activity on G12C-mutant HRAS, NRAS, and KRAS, with little, if any, activity on KRASG13C.
RMC-4998 (0.1 μM) led to a faster disruption of the interaction between KRASG12C and CRAF compared with inactive state-selective inhibitors adagrasib (1 μM) and sotorasib (10 μM) in mutant KRAS in cancer cells.
RMC-4998 inhibits KRASG12C-driven tumor growth in vivo.

Physicochemical Properties

M.Wt	983.25
Formula	C57H74N8O7
Appearance	Solid
CAS No.
Storage	Solide Powder -20°C 12 Months; 4°C 6 Months	In Solvent -80°C 6 Months; -20°C 6 Months
Shipping
Solubility	10 mM in DMSO
Chemical Name/SMILES	2,7-Diazaspiro[4.4]nonane-2-acetamide, 7-[4-(dimethylamino)-4-methyl-1-oxo-2-pentyn-1-yl]-N-[(3R,9S,15S)-2-ethyl-2,4,5,6,9,10,11,12,15,16-decahydro-3-[2-[(1S)-1-methoxyethyl]-3-pyridinyl]-5,5-dimethyl-8,14-dioxo-8H,14H-1,22-etheno-9,13-imino-17,21-methenopyrrolo[3,4-r][1,7]oxaazacyclodocosin-15-yl]-α-(1-methylethyl)-1-oxo-, (αS,5S)-

References

1. Christopher J Schulze, et al. Science. 2023 Aug 18;381(6659):794-799.

RMC-4998 (RMC4998, RM-029)

Biological Activity

Physicochemical Properties

References

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