AMG 337 (C09-0735-527)

InformationAMG 337 AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the Met (c-Met) receptor with an IC50 of 1 nM.TargetsMET receptor (Cell-free assay); MET(H1094R) (Cell-free assay); MET(M1250T) (Cell-free assay); MET(V1092I) (Cell-free assay) 1 nM; 1 nM ;4.7 nM; 21.5 nMIn vitroAMG 337 potently inhibits the enzymatic activity of WT MET and a subset of MET mutants found in papillary renal cell carcinoma. The inability of AMG 337 to inhibit the Y1230 and D1228 mutants is likely the result of a disruption of the inactive confirmation of the activation loop in the MET kinase domain. AMG 337 also inhibits cell based HGF-induced MET phosphorylation in PC3 cells with IC50 of 5nM.AMG 337 inhibits proliferation in MET-dependent cancer cell lines. AMG 337 inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines resulting in profound effects on cell proliferation and survival.In vivoAMG 337 exhibits impressive potency with >90% inhibition of Gab-1 phosphorylation at a dose of 0.75 mg/kg (32 nmol/L free-drug concentration). AMG 337 is well tolerated at continuously administered doses that corresponded with complete MET inhibition for 24 hours, suggesting that AMG 337 has the preclinical attributes required to test the role of MET in human cancer.Cell Research(from reference)Cell lines：Human cancer cell lines Concentrations：serial dilution(a top concentration of 3 mmol/L.) Incubation Time：72 h. Specification: 0.98 Molecular Formula: C23H22FN7O3 Molecular Weight: 463.46 PubChem CID: 44181686 Isomeric SMILES: C[C@H](C1=NN=C2N1C=C(C=C2F)C3=CN(N=C3)C)N4C=CC5=C(C4=O)C=C(C=N5)OCCOC Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/A413926-SCI_1c8511dd0da9dae387606c9def4b1b71.pdf