Structure, functions, and recent advances in the development of SIRT2 inhibitors

Silent information regulators (sirtuins) are highly evolutionarily conserved and participate in many biological processes in the human body. Unlike classical histone deacetylases, the biological activity of sirtuins depends on nicotinamide adenine dinucleotide (NAD+). Among the seven human sirtuins, sirtuin 2 (SIRT2) is one of the most studied and plays important roles in cell aging, energy metabolism, and genome stability. SIRT2 dysregulation is closely associated with the development of cancer and neurodegenerative diseases. In this review, we summarize the structure, function, and recent developments in small-molecule inhibitors of SIRT2. We hope this review will aid the future development of new SIRT2 inhibitors.