Design, synthesis and structure–activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton
[Display omitted] Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synth...
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Veröffentlicht in: | Bioorganic & medicinal chemistry 2015-01, Vol.23 (2), p.328-339 |
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Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | [Display omitted]
Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synthesized a series of benzamide derivatives as SIRT2 inhibitor candidates. Among them, compound 17k showed the most potent SIRT2-inhibitory activity (IC50=0.60μM), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 >100μM). |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2014.11.027 |