In silico screening and identification of potential GSK3 beta inhibitors

摘要

Glycogen synthase kinase-3 beta (GSK3 beta) has been reported for its impact on multitude biological processes from cell proliferation to apoptosis. The increase in the ratio of active/inactive GSK3 beta is the major factor associated in the etiology of several psychiatric diseases, diabetes, muscle hypertrophy, neurodegenerative diseases, and some cancers. These findings made GSK3 beta 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 GSK3 beta 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 GSK3 beta. 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 GSK3 beta 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 GSK3 beta structures deposited in PDB.