Ki8751 is a selective and potent inhibitor of VEGFR2 with IC50 value of 0.9 nM [1].
VEGF receptors are receptors for vascular endothelial growth factor (VEGF) and regulate angiogenesis [2].
In cell-based assays, Ki8751 inhibited VEGFR2 with IC50 value of 0.9 nM. And it also inhibited c-Kit (IC50 40 nM), PDGFRα(IC50 67 nM), and FGFR-2 (IC50 170 nM) [1]. Treatment human umbilical vein endothelial cells (HUVECs) with Ki8751 (0.01, 0.1, 1, 10, 100 nM) caused inhibition of HUVEC growth in a dose-dependent way and completely suppressed it at 1 nM [1]. In metastatic colorectal cancer (CRC) cells of MIP, RKO, SW620, and SW480, Ki8751 (10 nM) induced cellular senescence [2].
In nude mice using xenografts of human glioma GL07, human stomach carcinoma St-4, human lung carcinoma LC-6, human colon carcinoma DLD-1 and human melanoma A375 cells, Ki8751 inhibited tumor growth. In nude rats using LC-6 human tumor xenografts, Ki8751 inhibited tumor growth, but then tumor regrowth was observed [1].
References:
[1]. Kubo K, Shimizu T, Ohyama S, et al. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem, 2005, 48(5): 1359-1366.
[2]. Hasan MR, Ho SH, Owen DA, et al. Inhibition of VEGF induces cellular senescence in colorectal cancer cells. Int J Cancer, 2011, 129(9): 2115–2123.
