| Bioactivity | AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor, with an IC50 of 15.5 μM. | ||||||||||||
| Invitro | 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]. | ||||||||||||
| Name | AK-7 | ||||||||||||
| CAS | 420831-40-9 | ||||||||||||
| Formula | C19H21BrN2O3S | ||||||||||||
| Molar Mass | 437.35 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Taylor DM, et al. A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase. ACS Chem Biol. 2011 Jun 17;6(6):540-6. [2]. Chopra V, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. Cell Rep. 2012 Dec 27;2(6):1492-7. [3]. Szego EM, et al. Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3β/β-catenin pathway. Neurobiol Aging. 2017 Aug;56:7-16. |