GSK-3β Allosteric Inhibition: A Dead End or a New Pharmacological Frontier?

ABSTRACT: Most kinase inhibitors are designed to bind to highly homologous ATP-binding sites, which leads to promiscuity and possible off-target effects. Allostery is an alternative approach to pursuing selectivity. However, allostery is difficult to exploit due to the wide variety of underlying mechanisms and the potential involvement of long-range conformational effects that are difficult to pinpoint. GSK-3β is involved in several pathologies. This critical target has an ATP-binding site that is highly homologous with the orthosteric sites of other kinases. Unsurprisingly, there is also great similarity between the ATP-binding sites of GSK-3β and its isomer, which is not redundant and thus would benefit from selective inhibition. Allostery would also allow for a moderate and tunable inhibition, wh

SUBMITTER: Balboni B 

PROVIDER: S-EPMC10139115 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature