Identifying potential ligand molecules EGFR mediated TNBC targeting the kinase domain-identification of customized drugs through in silico methods
- PMID: 36873279
- PMCID: V体育ios版 - PMC9976054
- DOI: 10.4103/1735-5362.367792
Identifying potential ligand molecules EGFR mediated TNBC targeting the kinase domain-identification of customized drugs through VSports注册入口 - in silico methods
"VSports手机版" Abstract
Background and purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer in which three hormone receptors are negative. This work aimed at identifying customized potential molecules inhibiting epidermal growth factor receptor (EGFR) by exploring variants using the pharmacogenomics approaches VSports手机版. .
Experimental approach: The pharmacogenomics approach has been followed to identify the genetic variants across the 1000 genomes continental population. Model proteins for the populations have been designed by including genetic variants in the reported positions. The 3D structures of the mutated proteins have been generated through homology modeling. The kinase domain present in the parent and the model protein molecules has been investigated. The docking study has been performed with the protein molecules against the kinase inhibitors evaluated by the molecular dynamic simulation studies. Molecular evolution has been performed to generate the potential derivatives of these kinase inhibitors suitable for the conserved region of the kinase domain. This study considered variants within the kinase domain as the sensitive region and remaining residues as the conserved region V体育安卓版. .
Findings/results: The results reveal that few kinase inhibitors interact with the sensitive region V体育ios版. Among the derivatives of these kinase inhibitors molecules, the potential kinase inhibitor that interacts with the different population models has been identified. .
Conclusions and implications: This study encompasses the importance of genetic variants in drug action as well as in the design of customized drugs VSports最新版本. This research gives way to designing customized potential molecules inhibiting EGFR by exploring variants using the pharmacogenomics approaches. .
Keywords: Conserved region; EGFR; Kinase domain; Sensitive region; TNBC V体育平台登录. .
Copyright: © 2023 Research in Pharmaceutical Sciences VSports注册入口. .
Conflict of interest statement
The authors declared no conflict of interest in this study.
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References
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- Alkabban FM, Ferguson T. Breast Cancer. Treasure Island (FL): StatPearls Publishing; 2022. pp. 1–29. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482286/ - PubMed
-
- Selase A, Cynthia AD, Newman O, Williams A, Michael O. Palmatine sensitizes chemoresistant triple negative breast cancer cells via efflux inhibition of Multidrug resistant protein 1. Sci Afr. 2021;14:1, e01022–8. doi: 10.1016/j.sciaf.2021.e01022. - DOI
-
- Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res. 2018;8(5):1483–1507. doi: 10.1007/s13346-018-0551-3. - "V体育官网" DOI - PMC - PubMed
-
- Sepahdar Z, Miroliaei M, Bouzari S, Khalaj V, Salimi M. Surface engineering of Escherichia coli-derived OMVs as promising nano-carriers to target EGFR-overexpressing breast cancer cells. Front Pharmacol. 2021;12:1, 719289–16. doi: 10.3389/fphar.2021.719289. - DOI (VSports手机版) - PMC - PubMed
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