Glycogen synthase kinase-3β inhibitors as a novel promising target in the treatment of cancer: Medicinal chemistry perspective

Glycogen synthase kinase-3 beta (GSK-3β) is a desired pharmacological target for cancer treatment. Despite its role in the development of various cancers, any target directing GSK-3 inhibitors have not been authorized for cancer treatment. The therapeutic importance of this enzyme is reflected in its monitoring character in autophagy, genetic material mismatch correction, tumor development, and invasion, which justifies medication combinations. GSK-3 controls various cell processes, including metabolism, signaling, and structural proteins. It modulates programmed cell death-ligand 1 (PD-L1) by phosphorylating target pro-oncogenes. New evidence on GSK-3 as a modulator of the antineoplastic immune response further highlights the potential uses of new GSK-3β selective antagonists currently being tested in humans. Indole, indazole, oxadiazole, isothiazolidinedione, and morpholine congeners are the privileged heterocyclic nucleus in drug discovery. These scaffolds produced numerous biological activities in which anticancer is important. The structure activity relationship studies may support to explore the design and synthesis of potential scaffolds in short time period. Therefore, in the present review, we tried to explore the structural aspects of GSK-3β with their structure–activity relationship against various targets for developing potential compounds. The GSK3β antagonists in clinical and preclinical trials have been reviewed in this study. And we tried to explore the structural aspects of several GSK-3β inhibitors with their structure–activity relationship for developing potential anticancer compounds, which will aid scientists in developing more target-specific therapeutic compounds with lower toxicity in the future.