Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing.
| Autor: | Baig MH; Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Yousuf M; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India., Khan MI; Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Khan I; Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, BezmialemVakif University, Istanbul, Turkey., Ahmad I; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia., Alshahrani MY; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia., Hassan MI; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India., Dong JJ; Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in oncology [Front Oncol] 2022 May 26; Vol. 12, pp. 865454. Date of Electronic Publication: 2022 May 26 (Print Publication: 2022). |
| DOI: | 10.3389/fonc.2022.865454 |
| Abstrakt: | Cyclin-dependent kinases (CDKs) play significant roles in numerous physiological, and are considered an attractive drug target for cancer, neurodegenerative, and inflammatory diseases. In the present study, we have aimed to investigate the binding affinity and inhibitory potential of selonsertib toward CDK6. Using the drug repurposing approach, we performed molecular docking of selonsertib with CDK6 and observed a significant binding affinity. To ascertain, we further performed essential dynamics analysis and free energy calculation, which suggested the formation of a stable selonsertib-CDK6 complex. The in-silico findings were further experimentally validated. The recombinant CDK6 was expressed, purified, and treated with selonsertib. The binding affinity of selonsertib to CDK6 was estimated by fluorescence binding studies and enzyme inhibition assay. The results indicated an appreciable binding of selonsertib against CDK6, which subsequently inhibits its activity with a commendable IC Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Baig, Yousuf, Khan, Khan, Ahmad, Alshahrani, Hassan and Dong.) |
| Databáze: | MEDLINE |
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