AMG337 是有效的、ATP竞争性的、高度选择性的MET激酶抑制剂，IC50< 5 nM。

AMG-337 is an effective and highly specific ATP-competitive MET kinase inhibitor. In enzymatic assays, AMG-337 inhibits MET kinase activity (IC50:< 5 nM).

AMG 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 5 nM. 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[1].

AMG 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 preClinicalal attributes required to test the role of MET in human cancer[1].

To evaluate the effect of AMG 337 on viability, cells are seeded in 96-well plates at an optimal density to ensure proliferation throughout the duration of the experiments. Cells are treated for 72 hours with a 10-point, 3-fold, serial dilution of AMG 337 using a top concentration of 3 mmol/L. Viability is measured with the CellTiter-Glo Luminescent Cell Viability Assay.(Only for Reference)

1173699-31-4

C23H22FN7O3

463.473

AMG337

DMSO:40 mg/mL
Ethanol:95 mg/mL (204.98 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years