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Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

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dc.contributor.authorSanphanya K.
dc.contributor.authorWattanapitayakul S.K.
dc.contributor.authorPhowichit S.
dc.contributor.authorFokin V.V.
dc.contributor.authorVajragupta O.
dc.date.accessioned2021-04-05T03:33:04Z
dc.date.available2021-04-05T03:33:04Z
dc.date.issued2013
dc.date.issuedBE2556
dc.description.abstractWe 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.
dc.format.mimetypeapplication/pdf
dc.identifier.citationBioorganic and Medicinal Chemistry Letters. Vol 23, No.10 (2013), p.2962-2967
dc.identifier.doi10.1016/j.bmcl.2013.03.042
dc.identifier.issn0960894X
dc.identifier.other2-s2.0-84876669366
dc.identifier.urihttps://hdl.handle.net/20.500.14740/6658
dc.rights.holderมหาวิทยาลัยศรีนครินทรวิโรฒ
dc.subject.other6 indazolyl triazole derivative
dc.subject.otherAngiogenesis inhibitor
dc.subject.otherAntineoplastic agent
dc.subject.otherSorafenib
dc.subject.otherTriazole
dc.subject.otherUnclassified drug
dc.subject.otherVasculotropin receptor 2
dc.subject.otherAntiangiogenic activity
dc.subject.otherAntineoplastic activity
dc.subject.otherArticle
dc.subject.otherBinding affinity
dc.subject.otherBinding site
dc.subject.otherCancer cell culture
dc.subject.otherControlled study
dc.subject.otherCytotoxicity
dc.subject.otherDrug structure
dc.subject.otherEnzyme active site
dc.subject.otherEnzyme activity
dc.subject.otherHuman
dc.subject.otherHuman cell
dc.subject.otherHydrogen bond
dc.subject.otherMolecular docking
dc.subject.otherProtein phosphorylation
dc.subject.otherAntineoplastic Agents
dc.subject.otherCell Line, Tumor
dc.subject.otherCell Proliferation
dc.subject.otherDose-Response Relationship, Drug
dc.subject.otherDrug Screening Assays, Antitumor
dc.subject.otherHep G2 Cells
dc.subject.otherHuman Umbilical Vein Endothelial Cells
dc.subject.otherHumans
dc.subject.otherIndazoles
dc.subject.otherMCF-7 Cells
dc.subject.otherModels, Molecular
dc.subject.otherMolecular Structure
dc.subject.otherPhenylurea Compounds
dc.subject.otherProtein Kinase Inhibitors
dc.subject.otherStructure-Activity Relationship
dc.subject.otherVascular Endothelial Growth Factor Receptor-2
dc.titleNovel VEGFR-2 kinase inhibitors identified by the back-to-front approach
dc.typeArticle
dspace.entity.typePublication
swu.datasource.scopushttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84876669366&doi=10.1016%2fj.bmcl.2013.03.042&partnerID=40&md5=9a035e2d7ecf67b322e565ccf3e83e4a

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