Abstract
The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reacting aldehydes with amines. Four sensitive binders targeted VEGFR-2 were directly isolated from the library. Antitumor activity test in vitro and inhibition experiments toward angiogenesis were also carried out.
Keywords:
Drug discovery; Dynamic combinatorial chemistry; Enzyme inhibitors; Imine formation; Ligand separation.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemistry*
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Angiogenesis Inhibitors / pharmacology*
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Combinatorial Chemistry Techniques / methods
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Drug Discovery
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Humans
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Neoplasms / blood supply
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Neoplasms / drug therapy
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Neovascularization, Pathologic / drug therapy
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Small Molecule Libraries / chemistry*
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Small Molecule Libraries / pharmacology*
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Small Molecule Libraries
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Vascular Endothelial Growth Factor Receptor-2