Description

• A cell permeable, benzylsulfonamide that inhibits SIRT2 activity (IC 50 = 12.5μM through enzymatic assay) by targeting the SIRT2 nicotinamide binding site, but may also target SIRT1 and SIRT3 (IC 50 >40μM) with much less potency
• Western analysis illustrates that treatment with AK-1 (> 25μM) leads to an increase in acetylated tubulin
• AK-1 (1 to 10μM) 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 4μM similar to that of genetic SIRT2 inhibition, and also correlates with the negative regulation of sterol biosynthesis.