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5mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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Purity: ≥98%
AR-A014418 (AR 0133418; SN4521; GSK-3 inhibitor VIII; AR 014418) is a brand-new, potent, ATP-competitive, and selective GSK3 (Glycogen Synthase Kinase 3) inhibitor with potential for treating neurodegenerative diseases. In cell-free assays, it inhibits GSK3β with an IC50 and Ki of 104 nM and 38 nM, respectively, and has minimal effects on the 26 other kinases that were also tested. By preventing Notch1 expression through inhibition of GSK-3-mediated Notch1 expression, AR-A014418 also demonstrated strong antiproliferative activity in vitro in the treatment of pancreatic cancer cells.
Targets |
GSK-3β (Ki = 38 nM); GSK-3β (Ki = 38 nM)
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ln Vitro |
AR-A014418 inhibits tau phosphorylation at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein with IC50 of 2.7 μM, and protects cultured N2A cells from death induced by blocking PI3K/PKB pathway. AR-A014418 prevents neurodegeneration caused by beta-amyloid peptide in hippocampal slices.[1] While in NGP and SH-5Y-SY cells, AR-A014418 lowers neuroendocrine markers and inhibits the growth of neuroblastoma cells.[2]
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ln Vivo |
AR-A014418 (0–4 mg/kg, i.p.) delays the onset of symptoms, enhances motor function, slows the progression of the disease, and delays the endpoint of the disease in ALS mice with the G93A mutant human SOD1. [3] Additionally, AR-A014418 inhibits mice's acetic acid and formalin-induced nociception by altering the signaling of the NMDA and metabotropic receptors as well as the transmission of TNF- and IL-1 in the spinal cord.[4]
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Enzyme Assay |
Calcine/propidium iodide uptake is used to determine cell viability. Calcein AM is only taken up by dead cells and becomes orange-red fluorescent when it is cleaved by esterases found within living cells. In a nutshell, N2A cells are cultured in vitro for two days before being exposed to 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 hours. Then, 2 μM PI and 1 μM calcein-AM are incubated with N2A cells for 30 min. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl2, and the cells are observed using fluorescence microscopy with a Zeiss Axiovert 135 microscope. In at least three different experiments, three fields (chosen at random) are analyzed per well (~300 cells/field). The percentage of PI-positive cells compared to all other cells is used to measure cell death. After deducting the quantity of dead cells present in vehicle-treated cultures, specific cell death is calculated in every experiment.
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Cell Assay |
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.
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Animal Protocol |
First, 56 Tg mice are split up into four groups to study the effects of GSK-3 inhibition on the clinical symptoms, lifespan, and motor behavior function of ALS. 14 animals per group are given intraperitoneal injections of 0.5 mL of normal saline five times a week starting 60 days after birth, along with 0 μg (control group), 1 μg (group A), 2 μg (group B), or 4 μg (group C) of AR-A014418 per gram of mouse. At the endpoint outlined below, mice are sacrificed.
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References |
Molecular Formula |
C12H12N4O4S
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Molecular Weight |
308.3131
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Exact Mass |
308.05793
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Elemental Analysis |
C, 46.75; H, 3.92; N, 18.17; O, 20.76; S, 10.40
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CAS # |
487021-52-3
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Appearance |
Solid powder
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SMILES |
COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-]
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InChi Key |
YAEMHJKFIIIULI-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C12H12N4O4S/c1-20-9-4-2-8(3-5-9)6-13-11(17)15-12-14-7-10(21-12)16(18)19/h2-5,7H,6H2,1H3,(H2,13,14,15,17)
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Chemical Name |
1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)ure
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Synonyms |
GSK-3β Inhibitor VIII; GSK-3beta Inhibitor VIII; SN 4521; SN-4521; SN4521; AR-A014418; AR-A 014418; AR-A-014418; AR-AO-14418;
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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) |
DMSO: ~62 mg/mL (~201.1 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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Preparing Stock Solutions | 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 |
*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.
Growth inhibition by GSK-3 inhibitor AR-A014418 in neuroblastoma cells. Cancer Biol Ther. 2014 May;15(5):510-5. td> |
AR-A014418 attenuation of apoptosis inhibitor expression in NGP and SH-5Y-SY cells. td> |
Continuous treatment of AR-A014418 is required for growth suppression of NGP and SH-5Y-SY cells. td> |