title: Sirtuin modulators.
abstract: Members of the sirtuin family including the founding protein Sir2 in Saccharomyces cerevisiae have been linked to lifespan extension in simple organisms. This finding prompted evaluation of the role of Sir2 orthologues in many aging-associated conditions including neurodegeneration, type II diabetes and cancer. These studies have demonstrated that genetic and pharmacologic manipulation of sirtuin activity have beneficial effects in a surprisingly broad spectrum of aging-associated conditions suggesting that the Sir2-family of enzymes presents an attractive target for the development of pharmacological agents. While the initial model favored pharmacological activators of sirtuins as calorie restriction mimetics, it now appears that either activation or inhibition of sirtuins may be desirable for ameliorating disease depending on the pathological condition and the target tissue. In this chapter we review the development of pharmacological small molecule activators and inhibitors of the sirtuin family of enzymes.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Sumit S
authors: SS
authors: Mahajan
authors: Vid
authors: V
authors: Leko
authors: Julian A
authors: JA
authors: Simon
authors: Antonio
authors: A
authors: Bedalov
mesh_terms: D000818:Animals; D015195:Drug Design; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011487:Protein Conformation; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020536:Enzyme Activators; D056572:Histone Deacetylase Inhibitors; D037761:Sirtuins