AK-7 is a cell- and brain-permeable, selective sirtuin SIRT2 inhibitor (IC50 ~15.5 μM), displays no effect on SIRT1 or SIRT3. It diminishes neuronal cell death induced by mutant huntingtin fragment. It also down-regulates cholesterol biosynthetic gene expression and reduces total cholesterol levels in neurons in vivo. In two genetic mouse models of Huntington’s disease, AK-7 treatment resulted in improved motor function, extended survival, and reduced brain atrophy. AK-7 is a good chemical probe to study SIRT2’s roles in metabolic diseases, cancer, age-related disorders, and neurodegenerative diseases.?
How to Use:
In vitro: AK-7 was used at 10-25 μM in vitro and in cellular assays.
In vivo: AK-7 was administered by intraperitoneal injection to mice at 15-30 mg/kg/dose twice daily (formulation: 1.5 mg/mL in 25% Cremophor/10% DMSO in water).
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