AK-7 | SIRT2 inhibitor

AK-7 (420831-40-9) is a selective Sirt2 inhibitor (IC₅₀=15.5 μM) which does not inhibit Sirt1 or Sirt3.¹ It down regulates cholesterol biosynthesis genes in primary striatal neurons.¹ AK-7 displays neuroprotective effects in Huntington's disease mouse models including improved motor function, extended survival and reduced brain atrophy all of which were associated with reduced aggregated mutant huntingtin.²  Ameliorate β-amyloid pathology and cognitive impairment in an Alzheimer's disease model.³

References/Citations
1) Tylor et al. (2011), A brain-permeable small molecule that reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase; ACS Chem. Biol., 6 540
2) Chopra et al. (2012), The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models; Cell Rep., 2 1492
3) Wang et al. (2020) RTN4B-mediated suppression of Sirtuin 2 activity ameliorates ß-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model; Aging Cell, July 23 e13194