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.

For research use only. We do not sell to patients.

Specification

Synonym(s)	Met Kinase Inhibitor VI, SGX523, 6-(6-(1-Methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylthio)quinoline, SGX523
Empirical Formula (Hill Notation)	C18H13N7S
CAS Number	1022150-57-7
Molecular Weight	359.41
Purity	≥98%
form	powder
storage condition	OK to freeze protect from light
color	tan
solubility	DMSO: 2.5 mg/mL
shipped in	ambient
storage temp.	−20°C
InChI	1S/C18H13N7S/c1-24-11-13(10-20-24)16-6-7-17-21-22-18(25(17)23-16)26-14-4-5-15-12(9-14)3-2-8-19-15/h2-11H,1H3

SGX-523