期刊
CURRENT MEDICINAL CHEMISTRY
卷 18, 期 13, 页码 1936-1946出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986711795590057
关键词
Histone deacetylase; NAD(+); Sirtuin; Sirtuin inhibitor; Cancer therapy; Drug discovery; Drug design; high-throughput screening; virtual screening; phenotypic screening
资金
- Center for Drug Design in the Academic Health Center of the University of Minnesota
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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