The role of serum and glucocorticoid-regulated kinase 1 in cellular signaling: Implications for drug development

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a ubiquitously expressed protein belonging to the Ser/Thr kinase family. It regulates diverse physiological processes, including epithelial sodium channel activity, hypertension, cell proliferation, and insulin sensitivity. Due to its significant role in the pathogenesis of numerous diseases, SGK1 can be exploited as a potential therapeutic target to address challenging health problems. SGK1 is associated with the development of obesity, and its overexpression enhances the sodium-glucose co-transporter 1 activity, which absorbs intestinal glucose. This review highlighted the detailed functional significance of SGK1 signaling and role in different diseases and subsequent therapeutic targeting. We aim to provide deeper mechanistic insights into understanding the pathogenesis and recent advancements in the SGK1 targeted drug development process. Small-molecule inhibitors are being developed with excellent binding affinity and improved SGK1 inhibition with desired selectivity. We have discussed small molecule inhibitors designed explicitly as potent SGK1 inhibitors and their therapeutic implications in various diseases. We further addressed the therapeutic potential and mechanism of action of these SGK1 inhibitors and provided a strong scientific foundation for developing effective therapeutics.