Theranostics 2016; 6(4):571-593. doi:10.7150/thno.14334 This issue


Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging

Mukesh K. Pandey, Timothy R. DeGrado

Department of Radiology, Mayo Clinic, Rochester, MN, USA

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Pandey MK, DeGrado TR. Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging. Theranostics 2016; 6(4):571-593. doi:10.7150/thno.14334. Available from

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Graphic abstract

Glycogen synthase kinase-3 (GSK-3) is associated with various key biological processes, including glucose regulation, apoptosis, protein synthesis, cell signaling, cellular transport, gene transcription, proliferation, and intracellular communication. Accordingly, GSK-3 has been implicated in a wide variety of diseases and specifically targeted for both therapeutic and imaging applications by a large number of academic laboratories and pharmaceutical companies. Here, we review the structure, function, expression levels, and ligand-binding properties of GSK-3 and its connection to various diseases. A selected list of highly potent GSK-3 inhibitors, with IC50 <20 nM for adenosine triphosphate (ATP)-competitive inhibitors and IC50 <5 μM for non-ATP-competitive inhibitors, were analyzed for structure activity relationships. Furthermore, ubiquitous expression of GSK-3 and its possible impact on therapy and imaging are also highlighted. Finally, a rational perspective and possible route to selective and effective GSK-3 inhibitors is discussed.

Keywords: Glycogen synthase kinase-3, GSK-3 inhibitors