In silico screening and identification of potential GSK3β inhibitors

Abstract

Glycogen synthase kinase-3β (GSK3β) has been reported for its impact on multitude biological processes from cell proliferation to apoptosis. The increase in the ratio of active/inactive GSK3β is the major factor associated in the etiology of several psychiatric diseases, diabetes, muscle hypertrophy, neurodegenerative diseases, and some cancers. These findings made GSK3β a promising therapeutic target, and the interest in the discovery, synthesis of novel drugs to effectively attenuate its function with probably no side effects has been increasing in the chronology of GSK3β drug discovery. In the present study, we applied a combination of computational tools on a chemical library for the virtual discovery of their potency to inhibit GSK3β. The chemical library was screened against a set of filters at different levels. Finally, five compounds in the chemical library were found to potentially inhibit GSK3β with no toxic effects. Furthermore, binding mode analysis revealed that all the compounds bound to the ATP site and most of the hydrogen bonding interactions are conserved as in GSK3β structures deposited in PDB.

Keywords:

• Glycogen synthase kinase-3β
• virtual screening
• molecular docking
• ADME and toxicity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

DT is thankful to University Grants Commission, New Delhi for financial support in the form of UGC – BSR (RFSMS) Senior Research Fellowship. YS is thankful to Human Resource Development for Health Research, New Delhi (F.No.V0.25011/542-HRD/2016-HR).