| 名稱 | AR-A014418 |
| 描述 | AR-A014418 (GSK 3β inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor. |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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. |
| 體外活性 | AR-A014418通過(guò)調(diào)節(jié)NMDA和代謝型受體信號(hào)傳導(dǎo)以及在脊髓中的TNF-α和IL-1β傳遞,對(duì)乙酸和福爾馬林誘導(dǎo)的小鼠傷害感受產(chǎn)生抑制作用.在具有G93A突變型人SOD1的ALS小鼠模型中,AR-A014418（0-4 mg/kg,i.p.）延遲癥狀的發(fā)作,改善運(yùn)動(dòng)行為,減緩疾病進(jìn)展. |
| 體內(nèi)活性 | AR-A014418在NGP細(xì)胞和SH-5Y-SY細(xì)胞中,抑制神經(jīng)內(nèi)分泌標(biāo)志物,抑制神經(jīng)瘤細(xì)胞的生長(zhǎng)。AR-A014418抑制海馬切片中由β樣淀粉肽誘導(dǎo)的神經(jīng)退化。AR-A014418抑制表達(dá)人類(lèi)四重復(fù)tau蛋白的3T3成纖維細(xì)胞中的GSK3特異性位點(diǎn)（Ser-396）處的tau磷酸化,IC50為2.7 μM,并且保護(hù)培養(yǎng)的N2A細(xì)胞免于通過(guò)阻斷PI3K/PKB途徑誘導(dǎo)的死亡。 |
| 存儲(chǔ)條件 | 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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| 關(guān)鍵字 | 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 |
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