|Soluble in DMSO at 50 mg/mL or ethanol at 8 mg/mL.
The brain-permeable small-molecule AK-7 inhibits the NAD-dependent deacetylase sirtuin 2 (SirT2) which is involved in cytoskeletal regulation and progression through mitosis. The inhibitor AK-7 specifically binds and inhibits SirT2 (IC50 = 15.5 mM) and has no apparent effect on SirT1 or SirT3. AK-7 reduced total cholesterol in primary striatal neurons and reduced cholesterol in cultured naïve neuronal cells and brain slices from wild-type mice (1). Treatment with AK-7 improved motor function, extended survival, and reduced brain atrophy in a pair of genetic mouse models of Huntington’s disease (2). In a study of aging in a rat model of Parkinson's disease, AK-7 inhibition revealed a potential role for SirT2 in Parkinson's neurodegeneration, and suggested that AK-7 may have a beneficial neuroprotective effect (3). Similar results were seen in a mouse model of Parkinson's disease, but AK-7 was not able to counteract neurodegenerative processes associated with amyotrophic lateral sclerosis (ALS) or cerebral ischemia (4).
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