Welcome to ProbeChem!Global Supplier of Chemical Probes, Inhibitors & Agonists.
Chemical Structure : RMC-6291
CAS No.: 2641998-63-0
Catalog No.: PC-20608Not For Human Use, Lab Use Only.
RMC-6291 (RMC6291) is a potent, covalent, next-generation, mutant-selective inhibitor of active state KRAS G12C(ON) with IC50 of 0.7 nM (pERK), RMC-6291 forms a tri-complex within tumor cells between KRASG12C(ON) and cyclophilin A (CypA).
Bulk size, bulk discount!
E-mail: sales@probechem.com
Tech Support: tech@probechem.com
RMC-6291 (RMC6291) is a potent, covalent, next-generation, mutant-selective inhibitor of active state KRAS G12C(ON) with IC50 of 0.7 nM (pERK), RMC-6291 forms a tri-complex within tumor cells between KRASG12C(ON) and cyclophilin A (CypA).
RMC-6291 potently inhibits HCI-H358 cell growth (KRAS G12C) with IC50 of 0.09 nM, >10000-fold selectivity over WT cell.
RMC-6291 overcomes the limitations of first-generation KRASG12C(OFF) inhibitors in preclinical models by directly targeting the active form of KRAS G12C.
Oral administration of RMC-6291 produces deep and durable suppression of RAS pathway activity in KRASG12C tumor models and drives profound tumor regressions in vivo at well-tolerated doses.
RMC-6291 outperforms MRTX849 (Adagrasib, Cat. PC-72227), a KRASG12C(OFF) inhibitor, in mouse clinical trial consisting of multiple patient- and cell line-derived xenograft models of KRASG12C NSCLC.
Combination treatment with RMC-6291 and SHP2 or SOS1 inhibitors was well tolerated in preclinical models and further increased anti-tumor activity.
RMC-6291 also combined well with immune checkpoint inhibitors, sensitizing KRASG12C-bearing cancer models to anti-tumor immunity.
| M.Wt | 1012.28 | |
| Formula | C55H78FN9O8 | |
| Appearance | Solid | |
| Storage |
|
|
| Solubility |
10 mM in DMSO |
|
| Chemical Name/SMILES |
1-(4-(dimethylamino)-4-methylpent-2-ynoyl)-N-((2S)-1-(((22S,63S,4S)-11-ethyl-12-(2-((S)-1-methoxyethyl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-morpholina-1(5,3)-indola-6(1,3)-pyridazinacycloundecaphane-4-yl)amino)-3-methyl-1-oxobutan-2-yl)-4-fluoro-N-methylpiperidine-4-carboxamide |
|
1. Robert J. Nichols, et al. Cancer Res (2022) 82 (12_Supplement): 3595.
Copyright © 2022 probechem.com. All Rights Reserved. probechem Copyright
