SIRT2 Inhibitor II, AK-1

Toxicity: Standard Handling (A)

A cell permeable, benzylsulfonamide that inhibits SIRT2 activity (IC₅₀= 12.5 µM through enzymatic assay) by targeting the SIRT2 nicotinamide binding site, but may also target SIRT1 and SIRT3 (IC₅₀ >40 µM) with much less potency. Western analysis illustrates that treatment with AK-1 (>25 µM) leads to an increase in acetylated tubulin. AK-1 (1 to 10 µM) is shown to rescue neuronal dysfunction in two in vivo models of Huntington′s Disease (HD) in Dropshila and Caenorhabditis elegans. It also demonstrates recovery of neuronal toxicity in a primary model of HD from 1µM to 4 µM similar to that of genetic SIRT2 inhibition, and also correlates with the negative regulation of sterol biosynthesis.

Luthi-Carter, R., et al. 2010. Proc. Natl. Acad. Sci.107, 7927.
Outeiro, TF., et al. 2007. Science317, 516.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

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