AR-A014418 (Synonyms: AR-AO 14418;AR 0133418;AR 014418;GSK 3β inhibitor) |
| Catalog No.GC15425 |
A selective inhibitor of GSK3β
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 487021-52-3
Sample solution is provided at 25 µL, 10mM.
IC50: 104 ± 27 nM
Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer’s disease (AD). AR-A014418 is a selective GSK-3 inhibitor.
In vitro: ARA014418 acted as an ATP-competitive manner and did not significantly inhibit cdk2 or cdk5 or 26 other kinases demonstrating high specificity for GSK3. AR-A014418 inhibited tau phosphorylation at a GSK3-specific site (Ser-396) in cells stably expressing human four-repeat tau protein [1].
In vivo: ARA014418 induced behavioural changes that were consistent with the effects of antidepressant drugs. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, which was a well-established model for antidepressant efficacy. Moreover, the specificity of this effect was supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity [2].
Clinical trial: currently no clinical data were available.
References:
[1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Rades ter AC, Jerning E, Markgren PO, Borgeg rd T, Nyl f M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45.
[2] Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90.
| Kinase experiment [1]: | |
|
Kinase assays |
The competition experiments were carried out in duplicate with 10 concentrations of the inhibitor. The biotinylated peptide substrate was added at 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3, 12 mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β-mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serum albumin/25 μl and preincubated. The reaction was initiated by the addition of 0.04 μCi of [-33P]ATP and unlabeled ATP in 50 mM Mg(Ac)2 to a final concentration of 1 μM ATP and assay volume of 25 μl. After incubation for 20 min at room temperature, each reaction was terminated by the addition of 25 μl of stop solution containing 5 mM EDTA, 50 μM ATP, 0.1% Triton X-100, and 0.25 mg of streptavidin-coated SPA beads corresponding to 35 pmol of binding capacity. |
| Cell experiment [1]: | |
|
Cell lines |
3T3 fibroblasts were engineered to stably express four-repeat tau protein |
|
Preparation method |
The solubility of this compound in DMSO is >15.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
100 nM to 50 μM for 24 h |
|
Applications |
AR-A014418 could inhibit the tau phosphorylation at a GSK3-specific site in cells that were stably expressing human four-repeat tau protein. AR-A014418 could also protect N2A neuroblastoma cells against cell death, which was mediated through inhibition of the phosphatidylinositol 3-kinase/protein kinase B survival pathway. |
| Animal experiment [2]: | |
|
Animal models |
Male Sprague–Dawley rats |
|
Dosage form |
30 μmol/kg, i.p. |
|
Application |
The subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, a well-established model for antidepressant efficacy. In addition, the specificity of this effect was supported by the finding that AR-A014418 could decrease both spontaneous and amphetamine-induced activity. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Radester AC, Jerning E, Markgren PO, Borgegrd T, Nylf M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45. [2] Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90. | |
| Cas No. | 487021-52-3 | SDF | |
| Synonyms | AR-AO 14418;AR 0133418;AR 014418;GSK 3β inhibitor | ||
| Chemical Name | 1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)urea | ||
| Canonical SMILES | COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-] | ||
| Formula | C12H12N4O4S | M.Wt | 308.31 |
| Solubility | ≥ 15.4 mg/mL in DMSO | Storage | Store at -20°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 | 3.2435 mL | 16.2174 mL | 32.4349 mL |
| 5 mM | 0.6487 mL | 3.2435 mL | 6.487 mL |
| 10 mM | 0.3243 mL | 1.6217 mL | 3.2435 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 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 *