Sanders, Brandi D. published the artcileIdentification and characterization of novel sirtuin inhibitor scaffolds, HPLC of Formula: 1011557-82-6, the publication is Bioorganic & Medicinal Chemistry (2009), 17(19), 7031-7041, database is CAplus and MEDLINE.
The sirtuin proteins are broadly conserved NAD+-dependent deacetylases that are implicated in diverse biol. processes including DNA recombination and repair, transcriptional silencing, longevity, apoptosis, axonal protection, insulin signaling, and fat mobilization. Because of these associations, the identification of small mol. sirtuin modulators has been of significant interest. Here we report on high throughput screening against the yeast sirtuin, Hst2, leading to the identification of four unique inhibitor scaffolds that also inhibit the human sirtuins, SIRT1-3, and are able to inhibit telomeric silencing of yeast Sir2 in vivo. The identified inhibitor scaffolds range in potency from IC50 values of 6.5-130 μM against Hst2. Each of the inhibitor scaffolds binds reversibly to the enzyme, and kinetic anal. reveals that each of the inhibitors is non-competitive with respect to both acetyl-lysine and NAD+ binding. Limited SAR anal. of the scaffolds also identifies which functional groups may be important for inhibition. These sirtuin inhibitors are low mol. weight and well-suited for lead mol. optimization, making them useful chem. probes to study the mechanism and biol. roles of sirtuins and potential starting points for optimization into therapeutics.
Bioorganic & Medicinal Chemistry published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, HPLC of Formula: 1011557-82-6.
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