Structure-activity relationship (SAR) studies of synthetic glycogen synthase kinase-3β inhibitors: A critical review

Glycogen Synthase Kinase-3 (GSK-3) is a constitutively dynamic, omnipresent serine/threonine protein kinase regularly called as a "multitasking kinase" due to its pliable function in diverse signaling pathways. It exists in two isoforms i.e., GSK-3α and GSK-3β. Inhibition of GSK-3 may be useful in curing various diseases such as Alzheimer's disease, type II diabetes, mood disorders, cancers, chronic inflammatory agents, stroke, bipolar disorders and so on, but the approach poses significant challenges. Lithium was the first GSK-3β inhibitor to be used for therapeutic outcome and has been effectively used for many years. In recent years, a large number of structurally diverse potent GSK-3β inhibitors are reported. The present review focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potent GSK-3β inhibitors and also describes its structure-activity relationships (SAR) and molecular binding interactions of favorable applicability in various diseases.