Ki8751 (228559-41-9) is a very potent (IC50 = 0.9 nM) inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2).1 It also inhibited PDGFRα (IC50 = 67 nM), c-Kit (IC50 = 40 nM), and FGFR2 (IC50 = 170 nM). Ki8751 completely suppressed HUVEC growth at 1 nM. Ki8751 completely inhibited tumor growth in LC-6 human tumor xenografts @ 5mg/kg. Ki8751 displayed anti-influenza A and B activity via disruption of virus entry in a PDGFR/GM3-dependent manner.2
KI 8751 is a potent and selective inhibitor of VEGFR-2-tyrosine kinase which inhibits proliferation of human umbilical vein endothelial cells and inhibits tumor growth.
Ki8751 is a potent and selective inhibitor of VEGFR2, PDGFRα and c-Kit with IC50 of 0.9 nM, 67 nM and 40 nM, respectively.
ChEBI: 1-(2,4-difluorophenyl)-3-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]-2-fluorophenyl]urea is an aromatic ether.
A cell-permeable quinolyloxyphenyl-urea compound that acts as a VEGFR-2-selective inhibitior in both cell-based (IC50 = 0.9 nM in VEGF-induced receptor phosphorylation) and cell-free (IC50 = 4.0 nM in kinase reactions) assays. It inhibits c-Kit, PDGFRα, and FGFR-2 only at much higher concentrations (IC50 = 40, 67, and 170 nM, respectively, in cell-based assays), while exhibiting no effect against eight other commonly studied receptor and non-receptor kinases even at concentrations as high as 10 μM. Effectively blocks VEGF-dependent, but not VEGF-independent, cell proliferation in vitro and tumor growth in mice and rats (5 to 20 mg/kg, daily p.o.) in vivo.
Potent, selective inhibitor of VEGFR-2 tyrosine kinase (IC 50 = 0.9 nM). Displays some inhibitory activity towards c-Kit, PDGFR α and FGFR-2 (IC 50 values range from 40 to 170 nM) but is highly selective over other receptor tyrosine kinases (IC 50 > 10000 nM for FGFR-2, EGFR and HGFR). Inhibits VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) and inhibits tumor growth in vivo ; antiangiogenic.
[1] KAZUO KUBO. 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]. Journal of Medicinal Chemistry, 2005, 48 5: 1359-1366. DOI:
10.1021/jm030427r[2] PIETER VRIJENS. Influenza virus entry via the GM3 ganglioside-mediated platelet-derived growth factor receptor β signalling pathway.[J]. The Journal of general virology, 2019: 583-601. DOI:
10.1099/jgv.0.001235
