Conditionnement : 10mg
Téléphone : +1 850 650 7790
Synonyms: GSK-3beta Inhibitor VIII, GSK 3β inhibitor VIII, AR 014418, AR 0133418
| Description | AR-A014418 (GSK 3β inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor. |
| Targets & IC50 | GSK-3β:38 nM(Ki) |
| In vitro | AR-A014418 inhibited neuroendocrine markers and inhibited the growth of neuroma cells in NGP cells and SH-5Y-SY cells.AR-A014418 inhibited neurodegeneration induced by β-like amyloid peptide in hippocampal slices.AR-A014418 inhibited the expression of tau in 3T3 fibroblasts expressing human four-repeat tau proteins at the GSK3-specific locus (Ser AR-A014418 inhibited tau phosphorylation at the GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human tetra-repeat tau protein with an IC50 of 2.7 μM and protected cultured N2A cells from death induced by blocking the PI3K/PKB pathway. |
| In vivo | AR-A014418 inhibited neuroendocrine markers and inhibited the growth of neuroma cells in NGP cells and SH-5Y-SY cells.AR-A014418 inhibited neurodegeneration induced by β-like amyloid peptide in hippocampal slices.AR-A014418 inhibited the expression of tau in 3T3 fibroblasts expressing human four-repeat tau proteins at the GSK3-specific locus (Ser AR-A014418 inhibited tau phosphorylation at the GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human tetra-repeat tau protein with an IC50 of 2.7 μM and protected cultured N2A cells from death induced by blocking the PI3K/PKB pathway. |
| Synonyms | GSK-3beta Inhibitor VIII, GSK 3β inhibitor VIII, AR 014418, AR 0133418 |
| Kinase Assay | GSK3 Scintillation Proximity Assay: The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor in clear-bottomed microtiter plates. The biotinylated peptide substrate, biotin-AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 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 for 10-15 min. The reaction is initiated by the addition of 0.04 μCi of [γ-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. Blank controls without peptide substrate are used. After incubation for 20 min at room temperature, each reaction is 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. After 6 h the radioactivity is determined in a liquid scintillation counter. Inhibition curves are analyzed by non-linear regression using GraphPad Prism. |
| Cell Research | Cell viability is assessed by calcein/propidium iodide uptake. Calcein AM is taken up and cleaved by esterases present within living cells, yielding yellowish-green fluorescence, whereas PI is only taken up by dead cells, which become orange-red fluorescent. In brief, N2A cells are cultured for 2 days in vitro and then treated with 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 h. Subsequently, N2A cells are incubated for 30 min with 2 μM PI and 1 μM calcein-AM. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl2, and the cells are visualized by fluorescence microscopy using a Zeiss Axiovert 135 microscope. Three fields (selected at random) are analyzed per well (∼300 cells/field) in at least three different experiments. Cell death is expressed as percentage of PI-positive cells from the total number of cells. In every experiment, specific cell death is obtained after subtracting the number of dead cells present in vehicle-treated cultures. (Only for Reference) |
| Molecular Weight | 308.31 |
| Formula | C12H12N4O4S |
| Cas No. | 487021-52-3 |
| Smiles | COc1ccc(CNC(=O)Nc2ncc(s2)[N+]([O-])=O)cc1 |
| Relative Density. | 1.464g/cm3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year Shipping with blue ice/Shipping at ambient temperature. | |||||||||||||||||||||||||||||||||||
| Solubility Information | Ethanol: 1.5 mg/mL (4.87 mM), Sonication is recommended. DMSO: 30.8 mg/mL (99.9 mM), Sonication is recommended. | |||||||||||||||||||||||||||||||||||
| In Vivo Formulation | 10% DMSO+40% PEG300+5% Tween 80+45% Saline: 2 mg/mL (6.49 mM), Sonication is recommended. Please add the solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately. The formulation provided above is for reference purposes only. In vivo formulations may vary and should be modified based on specific experimental conditions. | |||||||||||||||||||||||||||||||||||
Solution Preparation Table | ||||||||||||||||||||||||||||||||||||
Ethanol/DMSO
DMSO
Note : The dilution table applies only to solid products. For liquid products, please calculate the stock solution based on the stated concentration and/or density. | ||||||||||||||||||||||||||||||||||||
For example, if the intended dosage is 10 mg/kg for animals weighing 20 g , with a dosing volume of 100 μL per animal, and a total of 10 animals are to be administered, using a formulation of 
10% DMSO+ 40% PEG300+ 5% Tween 80+ 45% Saline/PBS/ddH2O , the resulting working solution concentration would be 2 mg/mL.Dissolve 2 mg of the compound in 100 μL DMSO to obtain a stock solution at a concentration of 20 mg/mL . If the required concentration exceeds the compound's known solubility, please contact us for technical support before proceeding.
1) Add 100 μL of the DMSO stock solution to 400 µL PEG300 and mix thoroughly until the solution becomes clear.
2) Add 50 µL Tween 80 and mix well until fully clarified.
3) Add 450 µL Saline,PBS or ddH2O and mix thoroughly until a homogeneous solution is obtained.
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