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SIRT1 Inhibitor
No.167(October 2015)
- C2739
- 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (= Ex-527) (1) (*This product is discontinued.)
SIRT1 is a member of the sirtuin family of enzymes that catalyze the deacetylation of acetyl-lysine residues in histones and other proteins.1) SIRT1 plays an important role in a variety of processes including stress resistance, metabolism, differentiation, and aging.1) Sirtuins are the mammalian orthologues of the yeast Sir2 (silent information regulator 2).1,2) In the catalytic process of SIRT1, NAD+ is cleaved and O-acetyl ADP-ribose is generated.1,3,4)
Ex-527 (1) is a small molecule inhibitor of SIRT1 and possesses much higher selectivity for SIRT1 than others as shown below (Table).5) 1 also does not inhibit class I/II HDACs at concentrations up to 100 μM.6)
* Class I/II HDACs are histone deacetylases and remove acetyl groups without hydrolysis of NAD+.
Table. Sirtuin inhibitory activity of Ex-527 5)
This product is for research purpose only.
References
- 1) The SIR2 family of protein deacetylases
- 2) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
- 3) Structural identification of 2′- and 3′-O-acetyl-ADP-ribose as novel metabolites derived from the Sir2 family of β-NAD+-dependent histone/protein deacetylases
- 4) Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism
- 5) Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage
- 6) Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1
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