1. PI3K/Akt/mTOR
    Stem Cell/Wnt
  2. GSK-3

AR-A014418 (Synonyms: AR 0133418; GSK 3β inhibitor VIII; AR 014418)

Cat. No.: HY-10512 Purity: 97.22%
Handling Instructions

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor with an IC50 of 104 nM。

For research use only. We do not sell to patients.

AR-A014418 Chemical Structure

AR-A014418 Chemical Structure

CAS No. : 487021-52-3

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 65 In-stock
Estimated Time of Arrival: December 31
5 mg USD 59 In-stock
Estimated Time of Arrival: December 31
10 mg USD 89 In-stock
Estimated Time of Arrival: December 31
50 mg USD 255 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Top Publications Citing Use of Products

    AR-A014418 purchased from MCE. Usage Cited in: J Exp Clin Cancer Res. 2018 Jun 25;37(1):122.

    Treatment of MHCC97H cells with AR-A014418 for 24 h inhibits the expression of CD133, detected by RT-PCR.

    AR-A014418 purchased from MCE. Usage Cited in: Toxicol Sci. 2018 Apr 1;162(2):475-487.

    Inhibition of GSK-3β enhances demethylation of PP2Ac induced by MC-LR. SH-SY5Y cells are treated with 20 μM AR-A014418 for 4 h and then treated with 10 μM MC-LR for 24 h. Levels of DM-PP2Ac and PP2Ac are measured by Western blots.

    View All GSK-3 Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor with an IC50 of 104 nM。

    IC50 & Target

    GSK-3β

    104 nM (IC50)

    In Vitro

    AR-A014418 blocks the phosphorylation of tau at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein, with an IC50 of 2.7 μM, and protects cultured N2A cells from death cuased by PI3K/PKB pathway blockage. AR-A014418 also shows inhibitory effect on neurodegeneration mediated by beta-amyloid peptide in hippocampal slices[1]. AR-A014418 decreases neuroendocrine markers and suppresses neuroblastoma cell growth in NGP and SH-5Y-SY cells[2].

    In Vivo

    AR-A014418 (0-4 mg/kg, i.p.) delays the onset of symptoms, enhances motor activity, blocks disease progression, and postpons the endpoint of the disease in ALS mouse model with the G93A mutant human SOD1[3]. Furthermore, AR-A014418 suppresses acetic acid- and formalin-induced nociception in mice via modulating NMDA and metabotropic receptor signaling as well as TNF-α and IL-1β transmission in the spinal cord[4].

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (324.35 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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 6.4870 mL
    10 mM 0.3243 mL 1.6217 mL 3.2435 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (8.11 mM); Clear solution

    References
    Kinase Assay
    [1]

    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 appr 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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    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 (appr 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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    First, to examine the effects of GSK-3 inhibition on the clinical symptoms, life span, and motor behavior function of ALS, 56 Tg mice are divided into four groups. In each group, 0.5 mL of normal saline is mixed with either 0 μg (control group), 1 μg (group A), 2 μg (group B) or 4 μg (group C) of AR-A014418 per gram of mouse, and injected intraperitoneally into 14 animals per group 5 days a week beginning 60 days after birth. The mice are sacrificed at the endpoint described below.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    308.31

    Formula

    C₁₂H₁₂N₄O₄S

    CAS No.

    487021-52-3

    SMILES

    O=C(NCC1=CC=C(OC)C=C1)NC2=NC=C([N+]([O-])=O)S2

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

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    Product Name:
    AR-A014418
    Cat. No.:
    HY-10512
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    AR-A014418

    Cat. No.: HY-10512