AK-7 |
Katalog-Nr.GC10676 |
AK-7 ist ein selektiver zell- und gehirndurchlÄssiger SIRT2-Inhibitor mit einem IC50 von 15,5 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 420831-40-9
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: |
Neuronal nuclear antigen (NeuN)-positive neurons and some astroglia are derived from mechanically dissociated ganglionic eminences of E16 rat embryos. The HD model is based on the expression of mutant huntingtin. Treatments of cultures with AK-7 are at 10 μM for 24 h unless stated otherwise. DMSO is included at the same concentrations as a control. Lower dose, chronic treatments with AK-7 are introduced to neurons at DIV4 and continued weekly coinciding with normal medium change[1]. |
Animal experiment: |
AK-7, solubilized at 1.5 mg/mL in 25% Cremophor EL (BASF)/ 10% DMSO in water, is administered by intraperitoneal injection to 11 week old mice at 15 mg/kg/dose, and compound levels in serum and brain are measured following sacrifice. Blood is collected and centrifuged at 7,000 rpm for 7 min, and then serum is aspirated and immediately frozen in liquid nitrogen. Brains are immediately frozen in liquid nitrogen and stored at −80°C. Brains are weighed and then homogenized in four volumes of 10% Cremophor RH40 in water using a Polytron homogenizer, and 2% v/v phosphoric acid is added to the homogenate, vortexed, and centrifuged at 10,000 g at 25°C for 1 h. The supernatant is aspirated, and solid phase extraction is performed immediately. Serum samples are vortexed into 2% v/v phosphoric acid and centrifuged at 2500 rpm for 10 min[1]. |
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. |
AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor, with an IC50 of 15.5 μM.
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].
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].
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.
Cas No. | 420831-40-9 | SDF | |
Formula | C19H21BrN2O3S | M.Wt | 437.35 |
Löslichkeit | DMF: 15 mg/ml,DMF:PBS(pH7.2) (1:2): 0.3 mg/ml,DMSO: 5 mg/ml,Ethanol: 1 mg/ml | Storage | Store at 2-8°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.2865 mL | 11.4325 mL | 22.865 mL |
5 mM | 0.4573 mL | 2.2865 mL | 4.573 mL |
10 mM | 0.2286 mL | 1.1432 mL | 2.2865 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Average Rating: 5
(Based on Reviews and 19 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *