MK-2461

MK-2461 is an inhibitor of wild-type and mutant forms of c-MET (IC50s = 0.4-2 nM). It is selective for c-MET over a panel of 13 additional kinases (IC50s = 22-7,800 nM) but does inhibit Ron and FLT1 (IC50s = 7 and 10 nM, respectively). MK-2461 also inhibits autophosphorylation of FGFR2 and PDGFRalpha in KATO III cells but not EGF-induced phosphorylation of EGFR in A549 lung cancer cells when used at a concentration of 2 µM. It reduces proliferation in a panel of cancer cell lines, including cells expressing constitutively active c-MET, FGFR2, or PDGFR (IC50s = =1 µM for all). MKT-2461 (10-200 mg/kg) reduces tumor growth in a GTL-16 gastric cancer mouse xenograft model.Formal Name: N-[(2R)-1,4-dioxan-2-ylmethyl]-N-methyl-N'-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-sulfamide. CAS Number: 917879-39-1. Molecular Formula: C24H25N5O5S. Formula Weight: 495.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 30 mg/ml. lambdamax: 262, 346 nm. SMILES: O=C1C2=CC(C3=CN(N=C3)C)=CN=C2C=CC4=CC=C(NS(N(C)C[C@@H]5COCCO5)(=O)=O)C=C41. InChi Code: InChI=1S/C24H25N5O5S/c1-28-13-18(12-26-28)17-9-22-23(25-11-17)6-4-16-3-5-19(10-21(16)24(22)30)27-35(31,32)29(2)14-20-15-33-7-8-34-20/h3-6,9-13,20,27H,7-8,14-15H2,1-2H3/t20-/m1/s1. InChi Key: JGEBLDKNWBUGRZ-HXUWFJFHSA-N.