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Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery
The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the poten...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540634/ https://www.ncbi.nlm.nih.gov/pubmed/34685441 http://dx.doi.org/10.3390/life11101070 |
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author | Al-Sanea, Mohammad M. Chilingaryan, Garri Abelyan, Narek Sargsyan, Arsen Hovhannisyan, Sargis Gasparyan, Hayk Gevorgyan, Smbat Albogami, Sarah Ghoneim, Mohammed M. Farag, Ahmed K. Mohamed, Ahmed A. B. El-Damasy, Ashraf K. |
author_facet | Al-Sanea, Mohammad M. Chilingaryan, Garri Abelyan, Narek Sargsyan, Arsen Hovhannisyan, Sargis Gasparyan, Hayk Gevorgyan, Smbat Albogami, Sarah Ghoneim, Mohammed M. Farag, Ahmed K. Mohamed, Ahmed A. B. El-Damasy, Ashraf K. |
author_sort | Al-Sanea, Mohammad M. |
collection | PubMed |
description | The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). However, the endogenous and acquired resistance of the protein, toxicity of compounds and wide range of side effects still remain critical issues, which lead to the short-term clinical effects and failure of antiangiogenic drugs. We applied a combination of computational methods and approaches for drug design and discovery with the goal of finding novel, potential and small molecule inhibitors of VEGFR2, as alternatives to the known inhibitors’ chemical scaffolds and components. From studying several of these compounds, the derivatives of pyrido[1,2-a]pyrimidin-4-one and isoindoline-1,3-dione in particular were identified. |
format | Online Article Text |
id | pubmed-8540634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85406342021-10-24 Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery Al-Sanea, Mohammad M. Chilingaryan, Garri Abelyan, Narek Sargsyan, Arsen Hovhannisyan, Sargis Gasparyan, Hayk Gevorgyan, Smbat Albogami, Sarah Ghoneim, Mohammed M. Farag, Ahmed K. Mohamed, Ahmed A. B. El-Damasy, Ashraf K. Life (Basel) Article The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). However, the endogenous and acquired resistance of the protein, toxicity of compounds and wide range of side effects still remain critical issues, which lead to the short-term clinical effects and failure of antiangiogenic drugs. We applied a combination of computational methods and approaches for drug design and discovery with the goal of finding novel, potential and small molecule inhibitors of VEGFR2, as alternatives to the known inhibitors’ chemical scaffolds and components. From studying several of these compounds, the derivatives of pyrido[1,2-a]pyrimidin-4-one and isoindoline-1,3-dione in particular were identified. MDPI 2021-10-11 /pmc/articles/PMC8540634/ /pubmed/34685441 http://dx.doi.org/10.3390/life11101070 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Al-Sanea, Mohammad M. Chilingaryan, Garri Abelyan, Narek Sargsyan, Arsen Hovhannisyan, Sargis Gasparyan, Hayk Gevorgyan, Smbat Albogami, Sarah Ghoneim, Mohammed M. Farag, Ahmed K. Mohamed, Ahmed A. B. El-Damasy, Ashraf K. Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title | Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title_full | Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title_fullStr | Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title_full_unstemmed | Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title_short | Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery |
title_sort | identification of novel potential vegfr-2 inhibitors using a combination of computational methods for drug discovery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540634/ https://www.ncbi.nlm.nih.gov/pubmed/34685441 http://dx.doi.org/10.3390/life11101070 |
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