Target Validation Information
Target ID T80975
Target Name Vascular endothelial growth factor receptor 2
Target Type
Successful
Drug Potency against Target (3-Phenoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine Drug Info IC50 = 1410 nM [1]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info IC50 = 14400 nM [1]
4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 6300 nM [2]
4-Chloro-N-(2-methyl-benzoyl)-benzenesulfonamide Drug Info IC50 = 15000 nM [2]
AZD-1152-HQPA Drug Info Ki = 1800 nM [3]
CEP-11981 Drug Info Ki = 18 nM [4]
3-((3-bromothiophen-2-yl)methylene)indolin-2-one Drug Info IC50 = 15400 nM [5]
HKI-272 Drug Info IC50 = 858.2 nM [6]
Brivanib Drug Info Ki = 28 nM [7]
VATALANIB Drug Info IC50 = 30 nM [8]
3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info IC50 = 7600 nM [1]
(2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine Drug Info IC50 = 3260 nM [1]
SU-11652 Drug Info IC50 = 50 nM [9]
Phenyl-(5-phenyl-oxazol-2-yl)-amine Drug Info IC50 = 3000 nM [1]
[3-(5-Phenyl-oxazol-2-ylamino)-phenyl]-methanol Drug Info IC50 = 1650 nM [1]
TG-100435 Drug Info Ki = 784 nM [10]
Axitinib Drug Info IC50 = 0.2 nM [11]
XL880 Drug Info Ki = 0.86 nM [12]
SU-14813 Drug Info IC50 = 50 nM [13]
4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide Drug Info IC50 = 11000 nM [2]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole Drug Info IC50 = 3300 nM [14]
3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine Drug Info IC50 = 224 nM [15]
L000021649 Drug Info IC50 = 3 nM [15]
Ro-4396686 Drug Info IC50 = 50 nM [16]
2-(p-toluidino)-4-phenylpyrimidine-5-carbonitrile Drug Info IC50 = 1000 nM [17]
Vandetanib Drug Info IC50 = 40 nM [18]
Sunitinib Drug Info Ki = 80 nM [19]
4-phenyl-2-(phenylamino)pyrimidine-5-carbonitrile Drug Info IC50 = 1000 nM [17]
AG1295 Drug Info IC50 = 6200 nM [20]
WHI-P180 Drug Info IC50 = 50 nM [5]
CP-547632 Drug Info IC50 = 11 nM [21]
8-methyl-4H,7H-indolo[6,5,4-cd]indol-5-one Drug Info IC50 = 1000 nM [5]
OSI-930 Drug Info Ki = 9 nM [22]
(4-Phenoxy-phenyl)-quinazolin-4-yl-amine Drug Info IC50 = 2720 nM [23]
CB-676475 Drug Info IC50 = 1000 nM [24]
Motesanib Drug Info Ki = 3 nM [25]
3-(4-aminophenyl)thieno[3,2-c]pyridin-4-amine Drug Info IC50 = 4900 nM [26]
IM-023911 Drug Info IC50 = 190 nM [27]
4-(4-m-Tolylamino-phthalazin-1-yl)-benzamide Drug Info IC50 = 1600 nM [27]
3-(5-Thiophen-3-yl-pyridin-3-yl)-1H-indole Drug Info IC50 = 126 nM [28]
SU-6668 Drug Info Ki = 2100 nM [29]
3-(1H-Indol-2-yl)-1H-quinolin-2-one Drug Info IC50 = 8 nM [30]
6-(1H-Benzoimidazol-2-yl)-benzocyclohepten-7-one Drug Info IC50 = 355 nM [30]
4-(4-p-Tolylamino-phthalazin-1-yl)-benzamide Drug Info IC50 = 1800 nM [27]
4-(4-aminophenyl)-1H-indazol-3yl-amine Drug Info IC50 = 4790 nM [31]
PD-153035 Drug Info IC50 = 1489 nM [6]
3-phenyl-1,4-dihydroindeno[1,2-c]pyrazole Drug Info IC50 = 1200 nM [32]
VATALANIB Drug Info IC50 = 6754 nM [6]
BMS-536924 Drug Info IC50 = 1400 nM [33]
CEP-5104 Drug Info IC50 = 4175 nM [34]
BAY-57-9352 Drug Info Ki = 6 nM [35]
3-Benzimidazol-2-ylhydroquinolin-2-one Drug Info IC50 = 1700 nM [36]
4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide Drug Info IC50 = 4660 nM [1]
N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide Drug Info IC50 = 15000 nM [2]
(5-Phenyl-oxazol-2-yl)-m-tolyl-amine Drug Info IC50 = 1700 nM [1]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 14000 nM [2]
N-(2,4-Dichloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 530 nM [2]
4-Chloro-N-(2-chloro-benzoyl)-benzenesulfonamide Drug Info IC50 = 14000 nM [2]
Isoindolinone Urea derivative Drug Info IC50 = 18 nM [37]
BMS-645737 Drug Info IC50 = 53 nM [38]
Cediranib Drug Info IC50 < 1 nM [39]
6-o-tolylquinazolin-2-amine Drug Info IC50 = 4966 nM [40]
3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide Drug Info IC50 = 17000 nM [41]
5-(4-Methoxy-phenyl)-1-phenyl-1H-benzoimidazole Drug Info IC50 = 113 nM [42]
2-(pyrimidin-4-ylamino)thiazole-5-carbonitrile Drug Info IC50 = 990 nM [43]
KRN633 Drug Info IC50 = 1.16 nM [44]
Action against Disease Model Sunitinib In nine h uMan AML cell lines, sunitinib were potent inhibitor of cellular proliferation (IC50: 7~13,000 nM/L) [45] Drug Info
References
REF 1J 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 2J 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 3J Med Chem. 2007 May 3;50(9):2213-24. Epub 2007 Mar 21.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase.
REF 4CEP-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 5Bioorg Med Chem Lett. 2007 Apr 15;17(8):2126-33. Epub 2007 Feb 2.Pharmacophore modeling and in silico screening for new KDR kinase inhibitors.
REF 6Bioorg Med Chem. 2007 Jun 1;15(11):3635-48. Epub 2007 Mar 23.Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2.
REF 7J Med Chem. 2006 Apr 6;49(7):2143-6.Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor.
REF 8Recent advances in the development of multi-kinase inhibitors. Mini Rev Med Chem. 2008 Nov;8(13):1312-27.
REF 9J Med Chem. 2003 Mar 27;46(7):1116-9.Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase.
REF 10Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. Epub 2006 Nov 7.Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.
REF 11Nonclinical 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 12Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res. 2009 Oct 15;69(20):8009-16. doi: 10.1158/0008-5472.CAN-08-4889. Epub 2009 Oct 6.
REF 13A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
REF 14Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9. Epub 2006 Apr 5.Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases.
REF 15Bioorg Med Chem Lett. 2002 Dec 16;12(24):3537-41.Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics.
REF 16Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. Epub 2006 Feb 3.Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis.
REF 17Bioorg Med Chem Lett. 2007 Jun 15;17(12):3266-70. Epub 2007 Apr 10.4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: synthesis and biological evaluation.
REF 18Therapeutic potential of novel selective-spectrum kinase inhibitors in oncology. Expert Opin Investig Drugs. 2008 Jul;17(7):1013-28. doi: 10.1517/13543784.17.7.1013 .
REF 19BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):989-1000. doi: 10.1038/nrd2658.
REF 20Bioorg Med Chem. 2009 Oct 15;17(20):7324-36. Epub 2009 Aug 22.Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.
REF 21Small molecule inhibitors of KDR (VEGFR-2) kinase: an overview of structure activity relationships. Curr Top Med Chem. 2002 Sep;2(9):973-1000.
REF 22Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a novel thiophene kinase inhibitor OSI-930. Mol Cancer Ther. 2005 Aug;4(8):1186-97.
REF 23Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I.
REF 24Bioorg 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 25AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 2006 Sep 1;66(17):8715-21.
REF 26Bioorg Med Chem Lett. 2007 Mar 1;17(5):1246-9. Epub 2006 Dec 9.Thienopyridine urea inhibitors of KDR kinase.
REF 27Bioorg Med Chem Lett. 2005 Nov 1;15(21):4696-8.Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase.
REF 28Bioorg Med Chem Lett. 2003 Sep 15;13(18):2973-6.Discovery and evaluation of 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as a novel class of KDR kinase inhibitors.
REF 29SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 2000 Aug 1;60(15):4152-60.
REF 30Bioorg Med Chem Lett. 2004 Jan 19;14(2):351-5.Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmacokinetics and hERG binding.
REF 31J Med Chem. 2007 Apr 5;50(7):1584-97. Epub 2007 Mar 8.Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor.
REF 32Bioorg Med Chem Lett. 2006 Aug 15;16(16):4371-5. Epub 2006 Jun 5.Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors.
REF 33J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity.
REF 34J 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 35An overview of small-molecule inhibitors of VEGFR signaling. Nat Rev Clin Oncol. 2009 Oct;6(10):569-79. doi: 10.1038/nrclinonc.2009.130. Epub 2009 Sep 8.
REF 36J Med Chem. 2009 Jan 22;52(2):278-92.Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors.
REF 37Bioorg Med Chem Lett. 2004 Sep 6;14(17):4505-9.Isoindolinone ureas: a novel class of KDR kinase inhibitors.
REF 38Bioorg Med Chem Lett. 2008 May 1;18(9):2985-9. Epub 2008 Mar 22.Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor.
REF 39Molecular design and clinical development of VEGFR kinase inhibitors. Curr Top Med Chem. 2007;7(14):1379-93.
REF 40J Med Chem. 2006 Sep 21;49(19):5671-86.Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity.
REF 41Bioorg Med Chem Lett. 2006 Jan 1;16(1):96-9. Epub 2005 Oct 10.Scaffold oriented synthesis. Part 1: Design, preparation, and biological evaluation of thienopyrazoles as kinase inhibitors.
REF 42Bioorg Med Chem Lett. 2003 Aug 4;13(15):2485-8.Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR.
REF 43Bioorg Med Chem Lett. 2006 Mar 1;16(5):1146-50. Epub 2005 Dec 20.Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase.
REF 44Mol 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.
REF 45Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia. Mol Cancer Ther. 2008 May;7(5):1110-20. doi: 10.1158/1535-7163.MCT-07-2218.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.