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Glycogen synthase kinase-3β (GSK-3β) is a proline-directed serine/threonine kinase identified over 40 years ago. It is the key enzyme involved in glycogen biosynthesis and is expressed in all human tissues. Overexpression of GSK-3β is linked to several diseases, including diabetes mellitus, neurodegenerative disorders such as Alzheimer's disease, and cancer. Owing to its critical role in the pathophysiology of these diseases, GSK-3β has emerged as a validated and potential target for therapeutic intervention. In recent years, significant progress has been made in developing novel GSK-3 inhibitors. Some of these new inhibitors have shown promising results in treating some of these diseases.

This review covers patent literature on various GSK-3β inhibitors published between 2019 and 2024. This review also discusses the recent clinical developmental status of some of the promising GSK-3 inhibitors.

Although many heterocyclic compounds from natural as well as synthetic origin have shown promising inhibitory effects against GSK-3β, most of them have not yet progressed to the development stage. However, a critical review of their structures and biological profiles reveals significant potential for further development.