Abstract
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
Current Medicinal Chemistry
Title: Medicinal Chemistry of Sirtuin Inhibitors
Volume: 18 Issue: 13
Author(s): L. Chen
Affiliation:
Keywords: Histone deacetylase, NAD+, Sirtuin, Sirtuin inhibitor, Cancer therapy, Drug discovery, Drug design, high-throughput screening, virtual screening, phenotypic screening
Abstract: 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.
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Cite this article as:
Chen L., Medicinal Chemistry of Sirtuin Inhibitors, Current Medicinal Chemistry 2011; 18 (13) . https://dx.doi.org/10.2174/092986711795590057
DOI https://dx.doi.org/10.2174/092986711795590057 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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