GSK-3 inhibition: Achieving moderate efficacy with high selectivity |
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Authors: | Limor Avrahami Avital Licht-Murava Miriam Eisenstein Hagit Eldar-Finkelman |
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Institution: | 1. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;2. Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel |
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Abstract: | Inhibiting glycogen synthase kinase-3 (GSK-3) activity has become an attractive approach for treatment of neurodegenerative and psychiatric disorders. Diverse GSK-3 inhibitors have been reported and used in cellular and in vivo models. A major challenge, however, is achieving selectivity. In addition, it is increasingly recognized that a moderate inhibition of a cellular target, particularly for long-term treatment, provides more favorable outcome than complete inhibition. Substrate competitive inhibitors can fulfill the requirement for selectivity and allow fine tuning of the degree of inhibition. Here we describe the therapeutic potential of GSK-3 inhibitors and highlight our progress in the development of substrate competitive inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). |
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Keywords: | GSK-3 inhibitors CNS disorders Drug design L803-mts Alzheimer's disease |
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