Characterization of Small Molecules Inhibiting the Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1
| Autor: | David Sherris, Ming He, Allison B. Norvil, Qianyi Yang, Humaira Gowher |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Angiogenesis Kruppel-Like Transcription Factors Pharmaceutical Science Angiogenesis Inhibitors tube formation Article Analytical Chemistry Small Molecule Libraries lcsh:QD241-441 Mice Structure-Activity Relationship 03 medical and health sciences angiogenesis lcsh:Organic chemistry Drug Discovery Animals Viability assay Physical and Theoretical Chemistry Transcription factor Tube formation Zinc finger transcription factor Chemistry Organic Chemistry vascular biology DNA Small molecule endothelial cells 3. Good health Cell biology DNA-Binding Proteins Molecular Docking Simulation Endothelial stem cell DNA binding site MSS31 030104 developmental biology Gene Expression Regulation Chemistry (miscellaneous) Vezf1 Molecular Medicine Protein Binding Transcription Factors small molecule inhibitors computational modeling |
| Zdroj: | Molecules, Vol 23, Iss 7, p 1615 (2018) Molecules Volume 23 Issue 7 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry |
| ISSN: | 1420-3049 |
| Popis: | Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of anti-angiogenic therapies that treat various diseases, including cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20 &mu M. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases. |
| Databáze: | OpenAIRE |
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