| 名称 | AR-A014418 |
| 描述 | AR-A014418 (GSK 3β inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor. |
| 细胞实验 | 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) |
| 激酶实验 | 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. |
| 体外活性 | AR-A014418通过调节NMDA和代谢型受体信号传导以及在脊髓中的TNF-α和IL-1β传递,对乙酸和福尔马林诱导的小鼠伤害感受产生抑制作用.在具有G93A突变型人SOD1的ALS小鼠模型中,AR-A014418（0-4 mg/kg,i.p.）延迟症状的发作,改善运动行为,减缓疾病进展. |
| 体内活性 | AR-A014418在NGP细胞和SH-5Y-SY细胞中,抑制神经内分泌标志物,抑制神经瘤细胞的生长。AR-A014418抑制海马切片中由β样淀粉肽诱导的神经退化。AR-A014418抑制表达人类四重复tau蛋白的3T3成纤维细胞中的GSK3特异性位点（Ser-396）处的tau磷酸化,IC50为2.7 μM,并且保护培养的N2A细胞免于通过阻断PI3K/PKB途径诱导的死亡。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (6.49 mM), Sonication is recommended.
Ethanol : 1.5 mg/mL (4.87 mM), Sonication is recommended.
DMSO : 30.8 mg/mL (99.9 mM), Sonication is recommended.
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| 关键字 | Inhibitor | inhibit | GSK-3β Inhibitor VIII | GSK-3β | GSK-3b Inhibitor VIII | GSK-3 | GSK3 | GSK 3beta inhibitor VIII | GSK 3b inhibitor VIII | Glycogen synthase kinase-3 | Glycogen synthase kinase 3 | AR-A-014418 | AR-A014418 | ARA014418 | AR-A 014418 | AR-014418 | AR014418 | AR-0133418 | AR0133418 | AR A014418 |
| 相关产品 | Cromolyn sodium | Ginsenoside Rg2 | 4-Chloro-2'-bromoacetophenone | CHIR-99021 HCl | AT7519 | 5-Bromoindole | GSK-3 Inhibitor 5 | GSK 3 Inhibitor IX | SNS-032 | Cyanoacetohydrazide | CHIR-99021 | 1-Azakenpaullone |
| 相关库 | 抑制剂库 | 神经保护化合物库 | 经典已知活性库 | 已知活性化合物库 | 氧化还原化合物库 | 激酶抑制剂库 | 高选择性抑制剂库 | 抗衰老化合物库 | 抗肺癌化合物库 | 神经退行性疾病化合物库 | 膜蛋白靶向化合物库 | 免疫/炎症分子化合物库 |