Description
The sirtuin SIRT2 is a deacetylase which targets α-
tubulin, histone 4, forkhead transcription factors, and several other substrates. It has roles in metabolic diseases, cancer, age-
related disorders, and neurodegenerative diseases, potentially including Alzheimer’s, Huntington’s, and Parkinson’s diseases. AK-
7 is a cell-
and brain-
permeable inhibitor of SIRT2 (IC
50 = 15.5 μM). In culture, it diminishes neuronal cell death induced by mutant huntingtin fragment. In addition, AK-
7 down-
regulates cholesterol biosynthetic gene expression and reduces total cholesterol levels in neurons
in vivo.
Uses
AK-7 is a deacetylase which targets α-tubulin, histone 4, forkhead transcription factors, and several other substrates it is also a selective SIRT2 inhibitor.
References
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
