Target Validation Information
Target ID T07303
Target Name Vascular endothelial growth factor receptor 3
Target Type
Clinical Trial
Drug Potency against Target CEP-11981 Drug Info IC50 = 17 nM [552381]
[3-(5-Phenyl-oxazol-2-ylamino)-phenyl]-methanol Drug Info IC50 = 1650 nM [527458]
(5-Phenyl-oxazol-2-yl)-m-tolyl-amine Drug Info IC50 = 1700 nM [527458]
4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 6300 nM [527245]
4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide Drug Info IC50 = 11000 nM [527245]
N-(2,4-Dichloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 530 nM [527245]
Phenyl-(5-phenyl-oxazol-2-yl)-amine Drug Info IC50 = 3000 nM [527458]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info IC50 = 14400 nM [527458]
4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide Drug Info IC50 = 4660 nM [527458]
4-Chloro-N-(2-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 14000 nM [527245]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 14000 nM [527245]
4-Chloro-N-(2-methyl-benzoyl)-benzenesulfonamide Drug Info IC50 = 15000 nM [527245]
CEP-6331 Drug Info IC50 = 2459 nM [529647]
SU-14813 Drug Info IC50 = 15 nM [552773]
N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide Drug Info IC50 = 15000 nM [527245]
3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine Drug Info IC50 = 622 nM [526421]
Axitinib Drug Info IC50 = 0.1~0.3 nM [552885]
CB-676475 Drug Info IC50 = 1000 nM [527794]
Cediranib Drug Info IC50 < 1 nM [552727]
VATALANIB Drug Info IC50 = 100 nM [527458]
(2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine Drug Info IC50 = 3260 nM [527458]
3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info IC50 = 7600 nM [527458]
Motesanib Drug Info IC50 = 6 nM [552773]
KRN633 Drug Info IC50 = 50 nM [527373]
The Effect of Target Knockout, Knockdown or Genetic Variations The importance of the lymphangiogenic factor VEGF-D and its receptor VEGFR-3 in early lymphatic development remains largely unresolved. We therefore investigated their role in Xenopus laevis tadpoles, a small animal model allowing chemicogenetic dissection of developmental lymphangiogenesis. Single morpholino antisense oligo knockdown of xVEGF-D did not affect lymphatic commitment, but transiently impaired lymphatic endothelial cell (LEC) migration. Notably, combined knockdown of xVEGF-D with xVEGF-C at suboptimal morpholino concentrations resulted in more severe migration defects and lymphedema formation than the corresponding single knockdowns. Knockdown of VEGFR-3 or treatment with the VEGFR-3 inhibitor MAZ51 similarly impaired lymph vessel formation and function and caused pronounced edema. VEGFR-3 silencing by morpholino knockdown, MAZ51 treatment, or xVEGF-C/D double knockdown also resulted in dilation and dysfunction of the lymph heart. These findings doc uMent a critical role of VEGFR-3 in embryonic lymphatic development and function, and reveal a previously unrecognized modifier role of VEGF-D in the regulation of embryonic lymphangiogenesis in frog embryos. [552381]
References
Ref 552381CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Cancer Res. 2003 Sep 15;63(18):5978-91.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 529647J Med Chem. 2008 Sep 25;51(18):5680-9. Epub 2008 Aug 21.Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models.
Ref 552773A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
Ref 527245J Med Chem. 2004 Oct 21;47(22):5367-80.Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.
Ref 526421Bioorg Med Chem Lett. 2002 Oct 7;12(19):2767-70.Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: a new class of KDR kinase inhibitors.
Ref 552885Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83. doi: 10.1158/1078-0432.CCR-08-0652.
Ref 527794Bioorg Med Chem Lett. 2006 Jan 1;16(1):129-33. Epub 2005 Oct 10.Synthesis of a novel biotin-tagged photoaffinity probe for VEGF receptor tyrosine kinases.
Ref 552727Molecular design and clinical development of VEGFR kinase inhibitors. Curr Top Med Chem. 2007;7(14):1379-93.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 527458J Med Chem. 2005 Mar 10;48(5):1610-9.Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
Ref 552773A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
Ref 527373Mol Cancer Ther. 2004 Dec;3(12):1639-49.KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth.

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