For research use only. Not for therapeutic Use.
RMC-6291 is an orally active and covalent inhibitor of KRASG12C(ON). RMC-6291 forms a tri-complex within tumor cells between KRASG12C(ON) and cyclophilin A (CypA). Thus, RMC-6291 prevents KRASG12C(ON) from signaling via steric blockade of RAS effector binding. RMC-6291 inhibits ERK signaling and induced apoptosis in KRASG12C-mutant H358 cells. RMC-6291 also inhibits the proliferation of KRASG12C mutant cells with a median IC50 of 0.11 nM[1][2].
RMC-6291 (200mg/kg, p.o., qd for 60 d) significantly inhibits tumor growth and induce immunological memory in murine tumor models[3].
| Catalog Number | I041291 |
| CAS Number | 2641998-63-0 |
| Synonyms | 1-[4-(dimethylamino)-4-methylpent-2-ynoyl]-N-[(2S)-1-[[(6S,8S,14S)-22-ethyl-21-[2-[(1S)-1-methoxyethyl]pyridin-3-yl]-18,18-dimethyl-9,15-dioxo-5,16-dioxa-2,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),20,23(27),24-tetraen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-4-fluoro-N-methylpiperidine-4-carboxamide |
| Molecular Formula | C55H78FN9O8 |
| Purity | ≥95% |
| InChI | InChI=1S/C55H78FN9O8/c1-13-64-44-19-18-37-30-40(44)41(48(64)39-16-14-24-57-46(39)36(4)71-12)32-53(5,6)34-73-51(69)42-17-15-25-65(59-42)50(68)43(31-38-33-63(37)28-29-72-38)58-49(67)47(35(2)3)61(11)52(70)55(56)22-26-62(27-23-55)45(66)20-21-54(7,8)60(9)10/h14,16,18-19,24,30,35-36,38,42-43,47,59H,13,15,17,22-23,25-29,31-34H2,1-12H3,(H,58,67)/t36-,38-,42-,43-,47-/m0/s1 |
| InChIKey | HJNFYLSFWYRSHS-CMZSUCOPSA-N |
| SMILES | CCN1C2=C3C=C(C=C2)N4CCOC(C4)CC(C(=O)N5CCCC(N5)C(=O)OCC(CC3=C1C6=C(N=CC=C6)C(C)OC)(C)C)NC(=O)C(C(C)C)N(C)C(=O)C7(CCN(CC7)C(=O)C#CC(C)(C)N(C)C)F |
| Reference | [1]. Nichols R J, et al. RMC-6291, a next-generation tri-complex KRASG12C (ON) inhibitor, outperforms KRASG12C (OFF) inhibitors in preclinical models of KRASG12C cancers[J]. Cancer Research, 2022, 82(12_Supplement): 3595-3595. [2]. 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. [3]. Cristina Blaj, et al. Enhancement of anti-tumor immunity in immunogenic and immune-refractory RAS mutant tumors with tri-complex RAS(ON) inhibitors, revmed, #PB044, 2022 |
