GSK3 beta: role in therapeutic landscape and development of modulators

Glycogen synthase kinase-3 beta (GSK3 beta) is a multifunctional serine/threonine kinase which was originally identified as a regulator of glycogen metabolism. It plays a key role in the regulation of numerous signalling pathways including cellular process such as cell cycle, inflammation and cell proliferation. Over the last few years there is a considerable rise in the number of journals and patents publication by different workers worldwide. Many pharmaceutical companies are focusing on GSK3 beta as a therapeutic target for the treatment of disease conditions. The present review is focused on signalling pathways of different disease conditions where GSK3 beta is implicated. In this review, we present a comprehensive map of GSK3 beta signalling pathways in disease physiologies. Structural analysis of GSK3 beta along with molecular modelling reports from numerous workers are reviewed in context of design and development of GSK3 beta inhibitors. Patent landscape of the small molecule modulators is profiled. The chemo space for small molecule modulators extracted from public and proprietary Kinase Chembiobase for GSK3 beta are discussed. Compounds in different clinical phases of discovery are analysed. The review ends with the overall status of this important therapeutic target and challenges in development of its modulators.