Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing

Creative Commons License

Baig M. H., Yousuf M., Khan M. I., KHAN I., Ahmad I., Alshahrani M. Y., ...More

Frontiers in Oncology, vol.12, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12
  • Publication Date: 2022
  • Doi Number: 10.3389/fonc.2022.865454
  • Journal Name: Frontiers in Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
  • Keywords: drug repurposing, cyclin-dependent kinases, anticancer therapy, MD simulation, molecular docking, drug design and development
  • Bezmialem Vakıf University Affiliated: Yes


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.