Natural and synthetic bioactive inhibitors of glycogen synthase kinase.
Glycogen synthase kinase-3 is a multi-functional serine-threonine kinase and is involved in diverse physiological processes, including metabolism, cell cycle, and gene expression by regulating a wide variety of known substrates like glycogen synthase, tau-protein and β-catenin. Aberrant GSK-3 has been involved in diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. In this review, we present an overview of the involvement of GSK-3 in various signalling pathways, resulting in a number of adverse pathologies due to its dysregulation. In addition, a detailed description of the small molecule inhibitors of GSK-3 with different mode of action discovered or specifically developed for GSK-3 has been presented. Furthermore, some clues for the future optimization of these promising molecules to develop specific drugs inhibiting GSK-3, for the treatment of associated disease conditions have also been discussed.
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Imran
I
Khan
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Mushtaq A
MA
Tantray
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Mohammad Sarwar
MS
Alam
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: hhamid@jamiahamdard.ac.in.
Hinna
H
Hamid
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D055808:Drug Discovery; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010330:Patents as Topic; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D047428:Protein Kinase Inhibitors; D038362:Glycogen Synthase Kinase 3
ATP; Alzheimer's disease; Diabetes; Glycogen synthase kinase; Kinases; Phosphorylation