Tie2/VEGFR2 Kinase-IN-2

Tie2/VEGFR2 kinase-IN-2 is an inhibitor of tunica interna endothelial cell kinase 2 (Tie2) and VEGFR2 (IC50s = 13. and 7. nM, respectively). It is selective for Tie2 and VEGFR2 over Akt3, cyclin-dependent kinase 2 (Cdk2), EGFR, and glycogen synthase kinase 3 (GSK3, IC50s = >10,000, >10,000, 10,000, and 2,187 nM, respectively) but does inhibit VEGFR1 and VEGFR3 (IC50s = 8. and 7. nM, respectively). Tie2/VEGFR2 kinase-IN-2 inhibits VEGF-induced increases in the proliferation of human umbilical vein endothelial cells (HUVECs) and GM-CSF-induced increases in Tie2 autophosphorylation in NIH3T3 fibroblasts expressing chimeric CSF-1 receptor tyrosine kinase (FMS) and Tie2 receptors (IC50s = 2. and 18. nM, respectively). It reduces tumor volume and intratumoral vessel density in an HT-29 colon cancer mouse xenograft model when administered at doses of 3, 10, or 30 mg/kg per day. Tie2/VEGFR2 kinase-IN-2 (20 mg/kg) prevents decreases in body temperature in a mouse model of Tnf-alpha-induced lethal shock.. Solulibility: DMSO: Sparingly soluble: 1-10 mg/ml: Ethanol: Slightly soluble: 0.1-1 mg/ml.