Identification of a Novel Selective and Potent Inhibitor of Glycogen Synthase Kinase-3.

Identification of a Novel Selective and Potent Inhibitor of Glycogen Synthase Kinase-3. Am J Physiol Cell Physiol. 2019 Sep 25;: Authors: Noori MS, Bhatt PM, Courreges MC, Ghazanfari D, Cuckler C, Orac CM, McMills MC, Schwartz FL, Deosarkar SP, Bergmeier SC, McCall KD, Goetz DJ Abstract Glycogen synthase kinase-3 (GSK-3) is a multi-tasking protein kinase that regulates numerous critical cellular functions. Not surprisingly, elevated GSK-3 activity has been implicated in a host of diseases including pathological inflammation, diabetes, cancer, arthritis, asthma, bipolar disorder, and Alzheimer's. Therefore, reagents that inhibit GSK-3 activity provide a means to investigate the role of GSK-3 in cellular physiology and pathophysiology and could become valuable therapeutics. Finding a potent inhibitor of GSK-3 that can selectively target this kinase, amongst over 500 protein kinases in the human genome, is a significant challenge. Thus, there remains a critical need for the identification of selective inhibitors of GSK-3. In this work, we introduce a novel small organic compound, namely COB-187, which exhibits potent and highly selective inhibition of GSK-3. Specifically, this study (i) utilized a molecular screen of 414 kinase assays, representing 404 unique kinases, to reveal that COB-187 is a highly potent and selective inhibitor of GSK-3, (ii) utilized a cellular assay to reveal that COB-187 decreases the phosphorylation of canonica...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research