MRTX-849

MRTX-849 is a covalent inhibitor of K-RasG12C, a mutant form of K-Ras that accumulates in cancer cells. It binds to and stabilizes GDP-bound inactive K-RasG12C in an electrophoretic mobility shift assay when used at concentrations ranging from 2 to 15.6 nM. MRTX-849 (33-1,000 nM) reduces phosphorylation of the K-Ras targets ERK and S6 in MIA PaCa-2 cancer cells, which express K-RasG12C. In vivo, MRTX-849 (100 mg/kg) reduces tumor volume in 17 K-RasG12C-expressing lung, colon, pancreatic, cervical, and esophageal cancer mouse xenograft models but not wild-type K-Ras-expressing A549, HCT116, and H1299 mouse xenograft models.Formal Name: (2S)-4-[7-(8-chloro-1-naphthalenyl)-5,6,7,8-tetrahydro-2-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoro-1-oxo-2-propen-1-yl)-2-piperazineacetonitrile. CAS Number: 2326521-71-3. Molecular Formula: C32H35ClFN7O2. Formula Weight: 604.1. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMF:PBS (pH 7.2) (1:6): 0.14 mg/ml, DMSO: 1 mg/ml. lambdamax: 222 nm. SMILES: CN1CCC[C@H]1COC2=NC(N3C[C@@H](N(CC3)C(C(F)=C)=O)CC#N)=C4C(CN(C5=CC=CC6=C5C(Cl)=CC=C6)CC4)=N2. InChi Code: InChI=1S/C32H35ClFN7O2/c1-21(34)31(42)41-17-16-40(18-23(41)11-13-35)30-25-12-15-39(28-10-4-7-22-6-3-9-26(33)29(22)28)19-27(25)36-32(37-30)43-20-24-8-5-14-38(24)2/h3-4,6-7,9-10,23-24H,1,5,8,11-12,14-20H2,2H3/t23-,24-/m0/s1. InChi Key: PEMUGDMSUDYLHU-ZEQRLZLVSA-N.