| Identification | Back Directory | [Name]
RMC6291 | [CAS]
2641998-63-0 | [Synonyms]
RMC6291
3-Pyridazinecarboxylic acid, N1-[N-[[1-[4-(dimethylamino)-4-methyl-1-oxo-2-pentyn-1-yl]-4-fluoro-4-piperidinyl]carbonyl]-N-methyl-L-valyl-3-[4-[(2R)-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-2-[2-[(1S)-1-methoxyethyl]-3-pyridinyl]-1H-indol-5-yl]-2-morpholinyl]-L-alanyl]hexahydro-, (3→2)-lactone, (3S)… | [Molecular Formula]
C55H78FN9O8 | [MOL File]
2641998-63-0.mol | [Molecular Weight]
1012.28 |
| Chemical Properties | Back Directory | [density ]
1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [solubility ]
Acetonitrile: Slightly soluble: 0.1-1 mg/ml
DMSO: Sparingly soluble: 1-10 mg/ml | [form ]
Solid | [pka]
13.33±0.40(Predicted) | [color ]
White to off-white | [InChIKey]
HJNFYLSFWYRSHS-UHFFFAOYSA-N | [SMILES]
C(N1C2=CC=C3N4CCOC(CC(C(N5CCCC(N5)C(OCC(CC(C2=C3)=C1C1C=CC=NC=1C(C)OC)(C)C)=O)=O)NC(=O)C(C(C)C)N(C)C(C1(CCN(CC1)C(=O)C#CC(C)(C)N(C)C)F)=O)C4)C |
| Hazard Information | Back Directory | [Uses]
Elironrasib is an orally active and covalent inhibitor of KRASG12C(ON). Elironrasib forms a tri-complex within tumor cells between KRASG12C(ON) and cyclophilin A (CypA). Thus, Elironrasib prevents KRASG12C(ON) from signaling via steric blockade of RAS effector binding. Elironrasib inhibits ERK signaling and induced apoptosis in KRASG12C-mutant H358 cells. Elironrasib also inhibits the proliferation of KRASG12C mutant cells with a median IC50 of 0.11 nM[1][2]. | [in vivo]
Elironrasib (200mg/kg, p.o., qd for 60 d) significantly inhibits tumor growth and induce immunological memory in murine tumor models[3].
| [IC 50]
KRAS(G12C) | [References]
[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. DOI:10.1126/science.adg9652
[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 |
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