Design of a novel nucleoside analog as potent inhibitor of the NAD dependent deacetylase, SIRT2.

ABSTRACT: Sirtuins (class III histone deacetylase) are evolutionarily conserved NAD(+)-dependent enzymes that catalyze the deacetylation of acetyl-lysine residues of histones and other target proteins. Because of their associations in various pathophysiological conditions, the identification of small molecule modulators has been of significant interest. In the present study, virtual screening was carried out with NCI Diversity Set II using crystal structure of hSIRT2 (PDB ID: 1J8F) as a model for the docking procedure to find potential compounds, which were then subjected to experimental tests for their in vitro SIRT2 inhibitory activity. One of the 40 compounds tested, NSC671136 (IUPAC name: 6-Acetyl-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl 2,4-dichlorobenzoate) has

SUBMITTER: Sivaraman P 

PROVIDER: S-EPMC3065595 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature