In vitro activity: 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. 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. 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.

Cell Assay: BMMs are harvested, plated and 24-hrs later non-adherent cells were re-plated at a density of 20,000 cells/well in α-MEM/15%FBS/5% M-CSF. For determining cell proliferation, cells are treated with SRT2183 or a vehicle for 72 hours post plating and BrdU reagent is added 48 hrs post SRT2183 or vehicle administration according to the manufacturer's instructions to determine cell proliferation 3 days post plating.

Nature. 2007 Nov 29;450(7170):712-6; J Biol Chem. 2010 Mar 12;285(11):8340-51.