Current Trends in Sirtuin Activator and Inhibitor Development

被引：18

作者：

Bursch, Karina L. ^{[1
,2
]}

Goetz, Christopher J. ^{[1
]}

Smith, Brian C. ^{[1
,2
,3
]}

机构：

[1] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA

[2] Med Coll Wisconsin, Linda T & John A Mellowes Ctr Genom Sci & Precis M, Struct Genom Unit, Milwaukee, WI 53226 USA

[3] Med Coll Wisconsin, Program Chem Biol, Milwaukee, WI 53226 USA

来源：

MOLECULES | 2024年 / 29卷 / 05期

基金：

美国国家卫生研究院;

关键词：

sirtuins; epigenetics; lysine deacylation; drug development; EPSILON-THIOACETYL-LYSINE; SMALL-MOLECULE INHIBITOR; MECHANISM-BASED INHIBITORS; PEPTIDE-BASED POTENT; EXTENDS LIFE-SPAN; CELL-SURVIVAL; ACETYL-LYSINE; SELECTIVE INHIBITORS; STRUCTURAL BASIS; P53; ACETYLATION;

D O I：

10.3390/molecules29051185

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sirtuins are NAD+-dependent protein deacylases and key metabolic regulators, coupling the cellular energy state with selective lysine deacylation to regulate many downstream cellular processes. Humans encode seven sirtuin isoforms (Sirt1-7) with diverse subcellular localization and deacylase targets. Sirtuins are considered protective anti-aging proteins since increased sirtuin activity is canonically associated with lifespan extension and decreased activity with developing aging-related diseases. However, sirtuins can also assume detrimental cellular roles where increased activity contributes to pathophysiology. Modulation of sirtuin activity by activators and inhibitors thus holds substantial potential for defining the cellular roles of sirtuins in health and disease and developing therapeutics. Instead of being comprehensive, this review discusses the well-characterized sirtuin activators and inhibitors available to date, particularly those with demonstrated selectivity, potency, and cellular activity. This review also provides recommendations regarding the best-in-class sirtuin activators and inhibitors for practical research as sirtuin modulator discovery and refinement evolve.

引用

页数：38

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