| 名称 | AZD2858 |
| 描述 | AZD2858 is a selective GSK-3 inhibitor, inhibiting tau phosphorylation at the S396 site and activating Wnt signaling pathway. |
| 细胞实验 | Human adipose derived stem cells and rat MSCs (isolated from bone marrow of Sprague Dawley rats at less than 8 weeks after gestation) are cultured in a basal media of DMEM containing 5% FBS and 2 mM GlutaMax. Cells are seeded in basal media into 96-well plates (3–5000 cells/well) for 18 h before treatment with AZD2858 (0.3 nM to 20 mM). After 24 h, β-catenin stabilisation is measured.(Only for Reference) |
| 激酶实验 | Tau phosphorylation assay: NIH-3T3 cells expressing 4-repeat Tau are used to assess functional activity of AZD2858 in vitro. The cells are grown in DMEM media and 2 mM L-glut, and 10% HiFCS, and plated at a concentration of 6×105 cells/well in 6-well plates. In each experiment, AZD2858 is dosed in triplicates at a concentration of 1, 10, 100, 500, 1000, 2000 and 10,000 nM. Cells are treated for 4 h prior to cell lysis using 100 μL ice cold lysis buffer (0.5% NP-40, 10 mM Tris, pH 7.2, 150 mM NaCl, 2 mM EDTA). A suspension is made with addition of protease and phosphatase inhibitors: 50 mM NaF, 0.2 mM NaVO4 and Cocktail Protease inhibitors. The solution is then snap frozen at ? 80 °C for at least 1 h, before thawing on ice and lysate clarification by centrifugation, followed by Western blot according to standard protocols. After blocking, the blots are exposed to the primary antibody, Phospho-Ser396-tau (1:1000) over night, washed and incubated with the secondary antibody (donkey anti-rabbit, 1:5000), followed by a final wash. For re-probing, the primary antibody Tau5 (1:200) and the secondary horseradish peroxidase linked antibody (sheep anti-mouse, 1:10000) are used. All blots are developed using ECL Western blot detection reagents, Kodak X-ray films, quantified using densitometric analysis, and the ratio of S396 tau to total tau (tau5) is calculated. |
| 体外活性 | 30 μM/kg AZD2858处理大鼠三周后胼胝中矿物质密度(2周时28%,三周时38%)和矿物质含量(两周时81%,三周时93%)增加.大鼠用AZD2858处理28天后,血清中骨更新标志物产生时间依赖性变化,且骨密度增加.大鼠用AZD2858处理7天后,骨形成标志P1NP增加,溶蚀标志物TRAcP-5b降低,表明骨合成代谢增加,大鼠吸收减少.大鼠口服AZD2858治疗两周后,与对照组相比,引起骨密度剂量依赖增加,治疗两周后,在每天20 mg/kg(总BMC: 对照组的172%)剂量下具有最大疗效.AZD2858处理使骨折恢复更快,有骨性骨痂但没有明显的软骨成分. |
| 体内活性 | AZD2858在人类和大鼠间充质干细胞中引起β-连环蛋白稳定,激活体外成骨细胞和成骨矿化。初级分离的人成骨细胞样细胞上AZD2858处理（1 μM,12小时）导致β-连环蛋白水平增加3倍。 |
| 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 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 7 mg/mL (15.43 mM), Sonication is recommended.
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| 关键字 | Inhibitor | inhibit | GSK-3 | GSK3 | Glycogen synthase kinase-3 | Glycogen synthase kinase 3 | AZD-2858 | AZD2858 | AZD 2858 |
| 相关产品 | Cromolyn sodium | ROCK-IN-5 | 4-Methyl-6-Methoxycoumarin | Ginsenoside Rg2 | 4-Chloro-2'-bromoacetophenone | AT7519 | 5-Bromoindole | GSK-3 Inhibitor 5 | GSK 3 Inhibitor IX | SNS-032 | Indazole | Ethyl linoleate |
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