(R)-N-(2-(3-((3-hydroxypyrrolidin-1-yl)Methyl)iMidazo[2,1-b]thiazol-6-yl)phenyl)-2-naphthaMide

Uses

SRT 2183 is a selective Sirtuin-1 (SIRT1) activator with an EC1.5 value of 0.36 μM[1]. SRT 2183 induces growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and reduction of c-Myc protein levels[2].

Biological Activity

SRT2183 is a small molecule activator of the sirtuin protein isoform SIRT1.

in vitro

1-20 μM SRT2183 can effectively inhibit cell growth and apoptosis. It can cause increased mRNA levels of genes involved in pro-apoptosis, growth arrest, and DNA damage response. SRT1720, SRT2183, SRT1460 and resveratrol have multiple off-target effects on some receptors, enzymes, transporters and ion channels. They are not direct activators of SIRT1.

target

Target	Value
SIRT1

IC 50

SIRT1: 0.36 μM (EC1.5)

References

[1] Milne JC, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29; 450(7170): 712–716. DOI:10.1038/nature06261
[2] Scuto A, et al. SIRT1 activation enhances HDAC inhibition-mediated upregulation of GADD45G by repressing the binding of NF-κB/STAT3 complex to its promoter in malignant lymphoid cells. Cell Death Dis. 2013 May; 4(5): e635. DOI:10.1038/cddis.2013.159
[3] Gurt I, et al. The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391. DOI:10.1371/journal.pone.0134391