A review of developments in glycogen synthase kinase-3 regulators over the past 10 years

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that plays a pivotal role in regulating diverse cellular processes. It has been implicated in neurodegenerative diseases, diabetes, mood disorders, and cancer. Over the past few decades, significant progress has been made in developing various types of GSK-3 inhibitors and degradation agents. This review aims to provide a comprehensive overview of the current research landscape of clinical drugs targeting GSK-3, focusing on the structural characteristics and biological functions of GSK-3 inhibitors developed over the past decade. Additionally, it evaluates the advantages, disadvantages, and future trends associated with these different classes of inhibitors. Particular emphasis is placed on compounds currently under clinical evaluation and emerging strategies such as multi-target-directed ligands and proteolysis-targeting chimeras (PROTACs). This article offers valuable insights into the potential of GSK-3 as a therapeutic target.