SRT2183 is a small-molecule activator of the sirtuin subtype SIRT1, currently being developed by Sirtris Pharmaceuticals.
SRT2183 is potent with growth arrest and apoptosis induced at doses ranging from 1-20 μM. SRT2183 treatment leads to increased mRNA levels of pro-apoptosis, growth arrest, and DNA damage response genes[2]. SRT1720, SRT2183, SRT1460, and resveratrol exhibit multiple off-target activities against receptors, enzymes, transporters, and ion channels. They are not direct activators of SIRT1. SRT2183 has little or no effect on SIRT1 deacetylating activity with native full-length substrates[3]. SRT2183 activates AMPK, increases Sirt1 expression and decreases RelA/p65 lysine310 acetylation, critical for NF-κB activation, and an established Sirt1 target and inhibits RANKL-induced osteoclast generation and resorptive capacity in bone marrow macrophages[4].
[1] Milne JC, et al. Nature. 2007, 450(7170):712-6. [2] Anna Scuto, et al. Blood. 2009, 114:3083. [3] Pacholec M, et al. J Biol Chem. 2010, 285(11):8340-51.