Inhibition Of Tumor Cell Growth, Invasion, And Metastasis By Sim-89, A Novel Inhibitor Of Hgf Receptor Tyrosine Kinases

e13528 Background: The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a wide variety of human malignancies. SIM-89, developed by Simcere Bio-Pharmaceutical Co, Ltd, is a small-molecule kinase inhibitor that targets members of the HGF receptor tyrosine kinase families. Methods: Kinase inhibition was investigated using Z-lyte detection technique(Invitrogen), LanthaScreen Tb-activity technique and LanthaScreen Binding technique. Inhibition of p-Met and Met is validated through Westernblot. IC50 of the compound is determined by CCK-8. HGF level in culture medium is determined by ELISA.Migration and invasion assayare done with Transwell system. A549 and H460(2×106)are implanted subcutaneous in right upper extremity of nude mice.Once daily oral administration of SIM-89/ placebo are given to nude mice for 35d.Tumor growth curve is calculated. B16F10 tumor cells (2 × 105) were implanted via i.v. tail vein injection into mice on day 0. SIM-89/ pla...