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...
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MDPI AG
2021-10-01
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| author | Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Arsen Sargsyan Sargis Hovhannisyan Hayk Gasparyan Smbat Gevorgyan Sarah Albogami Mohammed M. Ghoneim Ahmed K. Farag Ahmed A. B. Mohamed Ashraf K. El-Damasy |
| author_facet | Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Arsen Sargsyan Sargis Hovhannisyan Hayk Gasparyan Smbat Gevorgyan Sarah Albogami Mohammed M. Ghoneim Ahmed K. Farag Ahmed A. B. Mohamed Ashraf K. El-Damasy |
| author_sort | Mohammad M. Al-Sanea |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:26:32Z |
| format | Article |
| id | doaj.art-05de75e3343848efb554cbb9eebcacc7 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T06:26:32Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-05de75e3343848efb554cbb9eebcacc72023-11-22T18:53:05ZengMDPI AGLife2075-17292021-10-011110107010.3390/life11101070Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug DiscoveryMohammad M. Al-Sanea0Garri Chilingaryan1Narek Abelyan2Arsen Sargsyan3Sargis Hovhannisyan4Hayk Gasparyan5Smbat Gevorgyan6Sarah Albogami7Mohammed M. Ghoneim8Ahmed K. Farag9Ahmed A. B. Mohamed10Ashraf K. El-Damasy11Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaInstitute of Molecular Biology of NAS RA, Yerevan 0014, ArmeniaInstitute of Biomedicine and Pharmacy, Russian-Armenian University, Yerevan 0051, ArmeniaInstitute of Molecular Biology of NAS RA, Yerevan 0014, ArmeniaDepartment of Mathematics and Mechanics, Yerevan State University, Yerevan 0025, ArmeniaDepartment of Mathematics and Mechanics, Yerevan State University, Yerevan 0025, ArmeniaFoundation for Armenian Science and Technology, Yerevan 0033, ArmeniaDepartment of Biotechnology, College of Science, Taif University, Taif 21944, Saudi ArabiaDepartment of Pharmacy Practice, College of Pharmacy, Al Maarefa University, Ad Diriyah 13713, Saudi ArabiaCurachem Inc., Cheongju-si 28161, KoreaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptThe 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.https://www.mdpi.com/2075-1729/11/10/1070VEGFR2tivozanibvirtual screeningdrug discoverymolecular dynamics simulations |
| spellingShingle | Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Arsen Sargsyan Sargis Hovhannisyan Hayk Gasparyan Smbat Gevorgyan Sarah Albogami Mohammed M. Ghoneim Ahmed K. Farag Ahmed A. B. Mohamed Ashraf K. El-Damasy Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery Life VEGFR2 tivozanib virtual screening drug discovery molecular dynamics simulations |
| 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 | VEGFR2 tivozanib virtual screening drug discovery molecular dynamics simulations |
| url | https://www.mdpi.com/2075-1729/11/10/1070 |
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