Serum- and glucocorticoid-induced kinase 1, a new therapeutic target for autophagy modulation in chronic diseases

Introduction: Autophagy, a basic cellular degradation pathway essential for survival, is altered both in aging and in many chronic human diseases, including infections, cancer, heart disease, and neurodegeneration. Identifying new therapeutic targets for the control and modulation of autophagy events is therefore of utmost importance in drug discovery. Serum and glucocorticoid activated kinase 1 (SGK1), known for decades for its role in ion channel modulation, is now known to act as a switch for autophagy homeostasis, and has emerged as a novel and important therapeutic target likely to attract considerable research attention in the coming years.Areas covered: In this general review of SGK1 we describe the kinase's structure and its roles in physiological and pathological contexts. We also discuss small-molecule modulators of SGK1 activity. These modulators are of particular interest to medicinal chemists and pharmacists seeking to develop more potent and selective drug candidates for SGK1, which, despite its key role in autophagy, remains relatively understudied.Expert opinion: The main future challenges in this area are (i) deciphering the role of SGK1 in selective autophagy processes (e.g. mitophagy, lipophagy, and aggrephagy); (ii) identifying selective allosteric modulators of SGK1 with specific biological functions; and (iii) conducting first-in-man clinical studies.