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AK-7

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Chemical Structure| 420831-40-9 同义名 : -
CAS号 : 420831-40-9
货号 : A566314
分子式 : C19H21BrN2O3S
纯度 : 99%+
分子量 : 437.351
MDL号 : MFCD03140195
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(114.32 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Sirtuin 2 is a member of the sirtuin family of proteins. It is a NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Sirtuin 2 participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. It also plays a major role in the control of cell cycle progression and genomic stability. AK-7 is a Sirtuin 2 selective inhibitor with IC50 of 15.5μM. At the concentration of 10μM, AK-7 reduced cholesterol levels in naive N2a neuroblastoma cells and hippocampal slice cultures from wild-type mice. At the concentration of 1μM , AK-7 showed neuroprotective effect in striatal Huntington’s disease neurons[3]. When i.p. administrated at the dose of 10mg/kg or 20mg/kg, AK-7 improved the behavior and neuropathological phenotype and extended survival of R6/2 HD mice. At the dose of 20mg/kg, AK-7 ameliorated HD neuropathology in R6/2 mice[4]. At the dose of 20mg/kg, i.p. administrated AK7 was neuroprotective in a subacute MPTP mouse model of Parkinson’s disease and significant increase of α-tubulin aectylation in the striatum after AK7 treatment was confirmed[5].
作用机制 AK-7 is a Sirtuin 2 selective inhibitor with a NAD+ competitive mechanism. The binding of AK-7 to Sirtuin 2 was suggested through docking calculations[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.29mL

0.46mL

0.23mL

11.43mL

2.29mL

1.14mL

22.86mL

4.57mL

2.29mL
参考文献

[1]Wang X, Guan Q, et al. Aging-related rotenone-induced neurochemical and behavioral deficits: role of SIRT2 and redox imbalance, and neuroprotection by AK-7. Drug Des Devel Ther. 2015 May 7;9:2553-63.

[2]Chopra V, Quinti L, 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]Taylor DM, Balabadra U, Xiang Z, Woodman B, Meade S, Amore A, Maxwell MM, Reeves S, Bates GP, Luthi-Carter R, Lowden PA, Kazantsev AG. 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.

[4]Chopra V, Quinti L, Kim J, Vollor L, Narayanan KL, Edgerly C, Cipicchio PM, Lauver MA, Choi SH, Silverman RB, Ferrante RJ, Hersch S, Kazantsev AG. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. Cell Rep. 2012 Dec 27;2(6):1492-7.

[5]Chen X, Wales P, Quinti L, Zuo F, Moniot S, Herisson F, Rauf NA, Wang H, Silverman RB, Ayata C, Maxwell MM, Steegborn C, Schwarzschild MA, Outeiro TF, Kazantsev AG. The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia. PLoS One. 2015 Jan 21;10(1):e0116919.