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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C21H23N7O3S |
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分子量 | 453.52 | CAS No. | 486424-20-8 | ||||
Solubility (25°C)* | 体外 | DMSO | 7 mg/mL (15.43 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, activating Wnt signaling, increases bone mass in rats. |
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in vitro | AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, inhibits tau phosphorylation at the S396 site, activates Wnt signaling pathway. AZD2858 treatment (1 μM, 12 h) on primary isolated human osteoblast-like cells results in a 3-fold increase of β-catenin levels. [1] AZD2858 causes β-catenin stabilisation in human and rat mesenchymal stem cells, stimulates hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. [2] |
in vivo | In rats, oral AZD2858 treatment causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control). A small but significant effect is also seen at cortical sites (total BMC: 111% of control). [1] AZD285 treatment (30 μmol/kg) on rats daily for up to 3 weeks shows an increase in both mineral density (of 28% at 2 weeks and 38% at 3 weeks) and mineral content (of 81% at 2 weeks and 93% at 3 weeks) in the calluses. AZD285 treatment makes the fractures heals more rapidly, with a bony callus without an obvious endochondral component. [3] AZD2858 produces time-dependent changes in serum bone turnover biomarkers and increases bone mass over 28 days exposure in rats. After 7 days, AZD2858 increases the bone formation biomarker P1NP, and reduces the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. [2] |
キナーゼアッセイ | Tau phosphorylation assay | |
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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. | ||
細胞アッセイ | 細胞株 | Human adipose derived stem cells and rat MSCs |
濃度 | ~20 mM | |
反応時間 | 24 h | |
実験の流れ | 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. | |
動物実験 | 動物モデル | rat |
投薬量 | 30 μmol/kg/day | |
投与方法 | orally |
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Data from [Data independently produced by , , FEBS Lett, 2016, 590(11):1614-29]
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The small molecule DIPQUO promotes osteogenic differentiation via inhibition of glycogen synthase kinase 3 β signaling [ J Biol Chem, 2021, S0021-9258(21)00485-3] | PubMed: 33895139 |
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] | PubMed: 31740922 |
Integrin alpha11 is an Osteolectin receptor and is required for the maintenance of adult skeletal bone mass. [ Elife, 2019, 10.7554/eLife.42274] | PubMed: 30632962 |
Predictions of genotoxic potential, mode of action, molecular targets, and potency via a tiered multiflow® assay data analysis strategy [ Environ Mol Mutagen, 2019, 60(6):513-533] | PubMed: 30702769 |
SFRP2 enhanced the adipogenic and neuronal differentiation potentials of stem cells from apical papilla. [Lin X, et al. Cell Biol Int, 2017, 41(5):534-543] | PubMed: 28244619 |
Investigating the Generalizability of the MultiFlow ® DNA Damage Assay and Several Companion Machine Learning Models With a Set of 103 Diverse Test Chemicals. [ Toxicol Sci, 2017, 162(1):146-166] | PubMed: 29106658 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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