title: Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging.
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.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: DeGrado
mesh_terms: D000818:Animals; D002468:Cell Physiological Phenomena; D003955:Diagnostic Tests, Routine; D004358:Drug Therapy / Q000379:methods; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3 inhibitors; Glycogen synthase kinase-3