figshare
Browse
tbsd_a_1900918_sm5077.pdf (4.21 MB)

Identification of selective cyclin-dependent kinase 2 inhibitor from the library of pyrrolone-fused benzosuberene compounds: an in silico exploration

Download (4.21 MB)
journal contribution
posted on 2021-03-22, 12:50 authored by Rahul Singh, Vijay Kumar Bhardwaj, Jatin Sharma, Pralay Das, Rituraj Purohit

The over-expression of cyclin-dependent kinase 2 is related to multiple cancers, which has led them to be a widely researched topic for nearly two decades. The prime focus of the present research is to design new potent and specific inhibitors against CDK2 to suppress cancer cell proliferation. In this study, we have chosen Flavopiridol, SU9516, and CVT-313 as standard inhibitors to compare with in-house synthesized pyrrolone-fused benzosuberene (PBS) compounds. We scrutinized Ligand2 as a selective inhibitor of CDK2 without off-target binding (CDK1 and CDK9) based on ligand efficiency and binding affinity. Interpretation of dynamic simulations and binding free energy studies unveiled that Ligand2 has a stable and equivalent free energy to standard inhibitors. These outcomes led towards positioning a potential natural molecule as selective inhibitor for CDK2 with low side effects.

Communicated by Ramaswamy H. Sarma

Funding

This work was supported by the Board of Research in Nuclear Sciences, Department of Atomic Energy, Mumbai, India vide letter No: 37(1)/14/26/2015/BRNS, the Department of Science and Technology, New Delhi, India SERB File No: ECR/2016/000031.

History

Usage metrics

    Journal of Biomolecular Structure and Dynamics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC