Khan Imran, Tantray Mushtaq A, Alam Mohammad Sarwar, Hamid Hinna
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Eur J Med Chem. 2017 Jan 5;125:464-477. doi: 10.1016/j.ejmech.2016.09.058. Epub 2016 Sep 20.
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.
糖原合酶激酶-3是一种多功能丝氨酸-苏氨酸激酶，通过调节多种已知底物，如糖原合酶、tau蛋白和β-连环蛋白，参与多种生理过程，包括代谢、细胞周期和基因表达。异常的糖原合酶激酶-3与糖尿病、炎症、癌症、阿尔茨海默病和双相情感障碍有关。在本综述中，我们概述了糖原合酶激酶-3参与的各种信号通路，由于其失调导致了许多不良病理状况。此外，还详细描述了已发现的或专门为糖原合酶激酶-3开发的具有不同作用模式的小分子抑制剂。此外，还讨论了未来优化这些有前景的分子以开发抑制糖原合酶激酶-3的特异性药物用于治疗相关疾病状况的一些线索。
