tcsc3223 AK-7

AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor, with an IC₅₀ of 15.5 μM.

IC50 & Target: IC50: 15.5 μM (SIRT2)^[1]

In Vitro: AK-7 (10 μM) reduces cholesterol levels in naive N2a neuroblastoma cells and hippocampal slice cultures from wild-type mice. AK-7 (1 μM) shows neuroprotective effect of AK-7 in striatal Huntington’s disease (HD) neurons^[1]. AK-7 (12.5 μM) decreases ratio of DA neurons in primary midbrain cultures^[3].

In Vivo: AK-7 (15 mg/kg/dose, i.p.) is brain-permeable in wild-type and HD mice^[1]. AK-7 (10, 20 mg/kg, i.p.) improves the behavior and neuropathological phenotype and extends survival of R6/2 HD mice. AK-7 (20 mg/kg) ameliorates HD neuropathology in R6/2 mice. AK-7 also reduces the polyglutamine aggregation in R6/2 brain. In addition, AK-7 treated 140CAG mice show motor performance changes that parallel untreated wild-type mice, with the 20 mg/kg dose being most effective and significantly different from untreated 140CAG mice^[2].