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. 2025 Mar 1:117:130074.
doi: 10.1016/j.bmcl.2024.130074. Epub 2024 Dec 16.

Docking and structure activity relationship studies of potent and selective thiazolidinethione GSK-3 inhibitors

Hannah Boesger  1 , Kurtis Williams  1 , Sa Adatu Abdullai  1 , Brianna Hubble  1 , Mahboubeh S Noori  2 , Crina Orac  1 , Deborah K Amesaki  1 , Davoud Ghazanfari  2 , Emily A Fairchild  1 , Opeyemi O Fatunbi  1 , Joshua A Pritchard  3 , Douglas J Goetz  4 , Jennifer V Hines  1 , Stephen C Bergmeier  5
Affiliations

Docking and structure activity relationship studies of potent and selective thiazolidinethione GSK-3 inhibitors

Hannah Boesger et al. Bioorg Med Chem Lett. .

Abstract

Glycogen synthase kinase-3 (GSK-3) plays a key role in several biochemical pathways and is an attractive target for pharmacological intervention. We prepared a series of analogs of a highly selective thiazolidinethione inhibitor of GSK-3. The structure-activity relationship indicated a precise structural requirement for potent inhibition. We used docking and bioinformatic analysis to explore the rationale for the potency and selectivity of this class of GSK-3 inhibitors. These computational studies identified residues unique to GSK-3 likely to play a role in ligand-specific induced fit interactions. Together, these studies highlight the structural stringency of specific kinase inhibition that can be achieved for GSK-3.

Keywords: Computational docking; GSK-3; Inhibitors; Thiazolidinethione.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Douglas Goetz reports financial support was provided by National Institutes of Health. Stephen C. Bergmeier has patent issued to Ohio University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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