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https://ir.swu.ac.th/jspui/handle/123456789/14067| Title: | Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach |
| Authors: | Sanphanya K. Wattanapitayakul S.K. Phowichit S. Fokin V.V. Vajragupta O. |
| Keywords: | 6 indazolyl triazole derivative angiogenesis inhibitor antineoplastic agent sorafenib triazole unclassified drug vasculotropin receptor 2 antiangiogenic activity antineoplastic activity article binding affinity binding site cancer cell culture controlled study cytotoxicity drug structure enzyme active site enzyme activity human human cell hydrogen bond molecular docking protein phosphorylation Antineoplastic Agents Cell Line, Tumor Cell Proliferation Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Hep G2 Cells Human Umbilical Vein Endothelial Cells Humans Indazoles MCF-7 Cells Models, Molecular Molecular Structure Phenylurea Compounds Protein Kinase Inhibitors Structure-Activity Relationship Vascular Endothelial Growth Factor Receptor-2 |
| Issue Date: | 2013 |
| Abstract: | We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1, 2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 μM. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 μM, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. © 2013 Elsevier Ltd. All rights reserved. |
| URI: | https://ir.swu.ac.th/jspui/handle/123456789/14067 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876669366&doi=10.1016%2fj.bmcl.2013.03.042&partnerID=40&md5=9a035e2d7ecf67b322e565ccf3e83e4a |
| ISSN: | 0960894X |
| Appears in Collections: | Scopus 1983-2021 |
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