Publication: Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing
No Thumbnail Available
Date
2022-05-26
Authors
Authors
Baig M. H.
Yousuf M.
Khan M. I.
KHAN I.
Ahmad I.
Alshahrani M. Y.
Hassan M. I.
Dong J.
Journal Title
Journal ISSN
Volume Title
Publisher
Metrics
Abstract
Copyright © 2022 Baig, Yousuf, Khan, Khan, Ahmad, Alshahrani, Hassan and Dong.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 IC50 value (9.8 μM). We concluded that targeting CDK6 by selonsertib can be an efficient therapeutic approach to cancer and other CDK6-related diseases. These observations provide a promising opportunity to utilize selonsertib to address CDK6-related human pathologies.
Description
Keywords
Tıp, Dahili Tıp Bilimleri, İç Hastalıkları, Onkoloji, Yaşam Bilimleri, Moleküler Biyoloji ve Genetik, Sitogenetik, Sağlık Bilimleri, Temel Bilimler, Medicine, Internal Medicine Sciences, Internal Diseases, Oncology, Life Sciences, Molecular Biology and Genetics, Cytogenetic, Health Sciences, Natural Sciences, Klinik Tıp (MED), Yaşam Bilimleri (LIFE), Klinik Tıp, ONKOLOJİ, BİYOKİMYA VE MOLEKÜLER BİYOLOJİ, Clinical Medicine (MED), Life Sciences (LIFE), CLINICAL MEDICINE, MOLECULAR BIOLOGY & GENETICS, ONCOLOGY, BIOCHEMISTRY & MOLECULAR BIOLOGY, Kanser Araştırmaları, Cancer Research, anticancer therapy, cyclin-dependent kinases, drug design and development, drug repurposing, MD simulation, molecular docking
Citation
Baig M. H., Yousuf M., Khan M. I., KHAN I., Ahmad I., Alshahrani M. Y., Hassan M. I., Dong J., "Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing", Frontiers in Oncology, cilt.12, 2022