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Purity: ≥98%
AK-7 (also known as AK7, CS-3223 and GL-8955) is a novel, selective, cell- and brain-permeable SITR2 inhibitor with the potential to be used for the treatment of Parkinson's disease and Huntington's disease (HD). It inihbits SIRT2 with an IC50 of 15.5 μM. AK-7 decreases brain atrophy and improves motor function in Huntington's disease models. Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Compound AK-7 treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. These results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.
| ln Vitro |
In both wild-type mouse hippocampus slice cultures and native N2a neuroblastoma cells, AK-7 (10 μM) lowers cholesterol levels. Neuroprotective effects of AK-7 (1 μM) on striatal neurons involved in Huntington's disease (HD) have been reported [1]. In primary midbrain cultures, the fraction of DA neurons is decreased by AK-7 (12.5 μM) [3].
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| ln Vivo |
In both wild-type and HD mice, AK-7 (15 mg/kg/dose, intraperitoneal) penetrates the brain [1]. In R6/2 HD mice, AK-7 (10, 20 mg/kg, intraperitoneally) prolongs survival and improves behavioral and neuropathological characteristics. In R6/2 mice, AK-7 (20 mg/kg) ameliorates HD neuropathology. In R6/2 brains, AK-7 also lessens polyglutamine aggregation. Additionally, the locomotor performance of 140CAG mice treated with AK-7 changed in a way that was comparable to that of untreated wild-type mice [2]. The most effective dose was 20 mg/kg, which also differed considerably from untreated 140CAG mice.
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| References |
[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 |
| Molecular Formula |
C19H21BRN2O3S
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| Molecular Weight |
437.35
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| CAS # |
420831-40-9
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| SMILES |
O=C(NC1=CC=CC(Br)=C1)C2=CC=CC(S(=O)(N3CCCCCC3)=O)=C2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2865 mL | 11.4325 mL | 22.8650 mL | |
| 5 mM | 0.4573 mL | 2.2865 mL | 4.5730 mL | |
| 10 mM | 0.2286 mL | 1.1432 mL | 2.2865 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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