| 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 | After three weeks of treatment with 30 μM/kg AZD2858, rats exhibited increases in bone callus mineral density (28% at 2 weeks, 38% at 3 weeks) and mineral content (81% at two weeks, 93% at three weeks). Treatment with AZD2858 for 28 days resulted in time-dependent changes in serum markers of bone turnover, along with an increase in bone density. Within 7 days of AZD2858 treatment, the bone formation marker P1NP increased, and the resorption marker TRAcP-5b decreased, indicating enhanced bone metabolism and reduced absorption in rats. Oral administration of AZD2858 for two weeks led to a dose-dependent increase in bone density compared to the control group, with the greatest efficacy observed at a daily dose of 20 mg/kg (total BMC: 172% of the control group). AZD2858 treatment expedited bone fracture healing, with the presence of a bony callus and no significant cartilage components. |
| 体内活性 | AZD2858 induces β-catenin stabilization in human and rat mesenchymal stem cells, activating osteoblasts and osteogenic mineralization in vitro. Treatment with AZD2858 (1 μM, 12 hours) on primary isolated human osteoblast-like cells results in a three-fold increase in β-catenin levels. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 7 mg/mL (15.43 mM)
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| 关键字 | AZD-2858 | Glycogen synthase kinase 3 | GSK-3 | Glycogen synthase kinase-3 | inhibit | Inhibitor | AZD2858 | AZD 2858 |
| 相关产品 | PHA-767491 | Cromolyn sodium | GSK 3 Inhibitor IX | CHIR-99021 | AT7519 | 5-Bromoindole | 4-Chloro-2'-bromoacetophenone | SNS-032 | CHIR-99021 HCl | GSK-3 Inhibitor 5 | MeBIO | 1-Azakenpaullone |
| 相关库 | 经典已知活性库 | 神经退行性疾病化合物库 | 激酶抑制剂库 | 抗乳腺癌化合物库 | 抗卵巢癌化合物库 | 抑制剂库 | 神经保护化合物库 | 抗前列腺癌化合物库 | 抗衰老化合物库 | 已知活性化合物库 |
United States
