In vitro activity: SKLB610 is a novel multi-targeted kinase inhibitor with more potent inhibition of VEGFR2. It has potential anticancer activity by potently suppressing human tumor angiogenesis. It inhibits angiogenesis-related tyrosine kinase VEGFR2, fibroblast growth factor receptor 2 (FGFR2) and platelet-derived growth factor receptor (PDGFR) at rate of 97%, 65% and 55%, respectively, at concentration of 10μM in biochemical kinase assays. In HUVECs, SKLB610 blocks VEGF stimulated phosphorylation of VEGFR2 in a dose dependent manner after SKLB610 treatment. SKLB610 significant inhibits HUVECs capillary tube formation in a concentration-dependent manner. Its potential to be a candidate of anticancer agent is worth being further investigated. S

Kinase Assay: KLB610 has a selective inhibition of VEGF-induced proliferation with an IC50 value of 2.2μM. In HUVECs, SKLB610 shows selectivity of 2-fold for inhibition of VEGF-induced proliferation versus bFGF-induced proliferation with an IC50 value of 4.7μM. In HUVECs, SKLB610 blocks VEGF stimulated phosphorylation of VEGFR2 in a dose dependent manner after SKLB610 treatment. SKLB610 significant inhibits HUVECs capillary tube formation in a concentration-dependent manner. SKLB610 inhibits the formation of vessel-like structures at 2.5 μM.

Cell Assay: KLB610 showed more selective inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) proliferation, and this proliferation inhibitory effect was associated with decreased phosphorylation of VEGFR2 and p42/44 mitogen-activated protein kinase (p42/44 MAPK).