Latham, AM, Kankanala, J, Fearnley, GW et al. (6 more authors) (2014) In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis. PLoS ONE, 9 (11). ARTN e110997. ISSN 1932-6203
Abstract
Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Latham et al. This is an Open Access article distributed in accordance with the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt, build upon this work, and license their derivative works on different terms, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Mar 2015 10:23 |
Last Modified: | 18 Jan 2018 05:01 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0110997 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.pone.0110997 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:84093 |