title: Sirtuin Inhibition: Strategies, Inhibitors, and Therapeutic Potential.
abstract: The β-NAD+-dependent Nε-acyl-lysine deacylation reaction catalyzed by sirtuin family members has been increasingly demonstrated to be important in regulating multiple crucial cellular processes and has also been proposed to be a therapeutic target for multiple human diseases. Accordingly, its inhibitors have been actively pursued over the past few years. In addition, we have also seen the pharmacological assessment of sirtuin inhibitory compounds, although to a lesser extent. In this review, we first discuss how sirtuin inhibitors were discovered with the use of various approaches. We then follow with a discussion of pharmacological studies using sirtuin inhibitors. Our aim here is to set a stage for developing future superior sirtuin inhibitors and for an expanded effort in exploiting inhibitors to explore and/or validate the therapeutic potential stemming from the inhibition of the sirtuin-catalyzed deacylation reaction.
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China. Electronic address: wzheng@ujs.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D037761:Sirtuins
keywords: cancer; chemical library screening; deacylation; mechanism-based; neurodegeneration; structure-based design