Medicinal Chemistry of Sirtuin Inhibitors

Author(s): L. Chen

Journal Name: Current Medicinal Chemistry

Volume 18 , Issue 13 , 2011

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As members of Class III histone deacetylases (HDACs), sirtuins use stoichiometric nicotinamide adenine dinucleotide (NAD+) to remove the acetyl group from N-acetyl-lysines of histones or non-histone proteins. Sirtuins have been implicated in metabolic diseases, cancer, and neurodegenerative diseases, constituting a promising target for drug discovery. While the early sirtuin inhibitors mimicked NAD+ or substrate peptides, high-throughput and in silico screenings have identified a wide range of core structures, many of which have been subjected to medicinal chemistry efforts. This review outlines inhibitor chemotypes, and their chemical modifications and biological evaluations, highlighting strategies to enhance inhibitory activity and selectivity among isoforms.

Keywords: Histone deacetylase, NAD+, Sirtuin, Sirtuin inhibitor, Cancer therapy, Drug discovery, Drug design, high-throughput screening, virtual screening, phenotypic screening

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Article Details

Year: 2011
Published on: 01 March, 2012
Page: [1936 - 1946]
Pages: 11
DOI: 10.2174/092986711795590057
Price: $65

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