Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784589034595549184
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
work_keys_str_mv AT alsaneamohammadm identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT chilingaryangarri identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT abelyannarek identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT sargsyanarsen identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT hovhannisyansargis identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT gasparyanhayk identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT gevorgyansmbat identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT albogamisarah identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT ghoneimmohammedm identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT faragahmedk identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT mohamedahmedab identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery
AT eldamasyashrafk identificationofnovelpotentialvegfr2inhibitorsusingacombinationofcomputationalmethodsfordrugdiscovery