Description General description A cell-permeable triazolopyridazine compound that acts as a potent, ATP-competitive (Ki = 2.7 & 23 nM using non-phosphorylated and phosphorylated MET kinase domain, respectively), and highly selective inhibitor against the tyrosine kinase activity of the HGF (hepatocyte growth factor) receptor c-MET (IC50 = 4 nM), while exhibiting little or no activity toward a panel of more than 210 other kinases, including the closely related RTK RON. Shown to inhibit the constitutive (IC50 = 40 nM in GTL16 cells) as well as HGF-stimulated (IC50 = 12 nM in A549 cells) MET autophosphorylation/activation in cultures in vitro and effectively suppress MET-dependent tumor growths in mice in vivo (twice daily oral dosings at 30 mg/kg). X-ray crystallography reveals that SGX523 locks MET in a "DFG-in" conformation with the triazolopyridazine moiety interacting with the hydrophobic side chains of Met1229 and Tyr1248, while Tyr1248 mutations are found to render MET insensitive to SGX523 inhibition both in cell-free and cell-based assays. Packaging 5 mg in Glass bottle Packaged under inert gas Warning Toxicity: Regulatory Review (Z) Reconstitution Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months -20°C. Other Notes Buchanan, S.G., et al. 2009. Mol. Cancer Ther.8, 3181. Eder, J.P., et al. 2009. Clin. Cancer Res.15, 2207.