AZD2858 |
| Catalog No.GC14736 |
AZD2858 est un puissant inhibiteur de GSK-3 actif par voie orale, avec des IC50 de 0,9 et 5 nM pour GSK-3α et GSK-3β, respectivement, utilisé dans la recherche sur la cicatrisation des fractures.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 486424-20-8
Sample solution is provided at 25 µL, 10mM.
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AZD2858 is a selective GSK-3 inhibitor with IC50 value of 68 nM.
Glycogen synthase kinase 3β (GSK-3β) plays an important role in the canonical Wnt pathway and participates in many biological processes [1].
In human osteoblast cells, AZD2858 increased β-catenin levels in a short time [1]. Incubation of hADSC with AZD2858 led to a significantly increase in osteogenic mineralisation. This indicated that inhibition of GSK-3 enhanced osteogenic differentiation of hADSC [2].
Treatment rats with AZD2858 orally increased trabecular bone mass in a dose-dependent way after a two-week treatment. The significant effect was also seen at cortical sites. Both vertebral compression strength and diaphyseal strength of femora increased in biomechanical testing. Furthermore, there was a dramatic increase in bone formation indices, serum markers of both bone formation and resorption were also elevated [1]. Also, AZD2858 drives mesenchymal cells into osteoblastic cells and leads to direct bone repair in an unstable fracture milieu [3].
References:
[1]. Marsell R, Sisask G, Nilsson Y, et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone, 2012, 50(3): 619-627.
[2]. Gilmour PS, O'Shea PJ, Fagura M, et al. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats. Toxicol Appl Pharmacol, 2013, 272(2): 399-407.
[3]. Sisask G, Marsell R, Sundgren-Andersson A, et al. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone, 2013, 54(1): 126-132.
Kinase experiment: | The potency of compounds at GSK-3β and cyclin-dependent protein kinase 2 (CDK2, kinase with closest homology to GSK-3β) is assessed using Z-LYTE™ Kinase assay kit in the presence of 7 and 80 μM ATP respectively. A ratiometric method is used to calculate the ratio of donor emission (445 nm) to acceptor emission (520 nm) after excitation of the donor fluorophore at 400 nm to quantitate the reaction progress. Kinase selectivity with AR79, AZD2858 and AZ13282107 are determined using the KinaseProfiler Service or University of Dundee Kinase. Over 80 different kinases are assessed at a single concentration of 1 or 10 μM of AR79, AZD2858 and AZ13282107. Concentration-inhibition 10-point curves to compounds that show activity are constructed to determine pIC50 estimations. Also, in some kinase assays these pIC50 estimations are converted to binding affinity values (pKi) using the Cheng-Prussoff equation to correct for the concentration of ATP used[3]. |
Animal experiment: | Each rat is dosed orally with vehicle or AZD2858 using a plastic gavage tube. The dose volume is 10 mL/kg. The vehicle consists of deionized water adjusted to pH 3.5±0.1. Formulations are adjusted to pH 3.5±0.1. The doses are 0, 0.2, 2 or 20 mg/kg respectively and administered either twice daily (TD), once daily (OD), every other day (O/2D), or every fourth day (O/4D) for 14 days. In total, the protocol results in 13 groups with 8 animals in each group (104 animals). At 7 days after the start of the study, and again 2 days prior to the scheduled terminal necropsy, each animal is injected subcutaneously with a bicarbonate buffered calcein solution (8 mg/kg, 1 mL/kg)[1]. |
References: [1]. Marsell R, et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone. 2012 Mar;50(3):619-27. | |
| Cas No. | 486424-20-8 | SDF | |
| Chemical Name | 3-amino-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-N-(pyridin-3-yl)pyrazine-2-carboxamide | ||
| Canonical SMILES | NC1=C(C(NC2=CC=CN=C2)=O)N=C(C3=CC=C(S(=O)(N4CCN(C)CC4)=O)C=C3)C=N1 | ||
| Formula | C21H23N7O3S | M.Wt | 453.52 |
| Solubility | ≥ 11.35mg/mL in DMSO | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.205 mL | 11.0249 mL | 22.0497 mL |
| 5 mM | 0.441 mL | 2.205 mL | 4.4099 mL |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.205 mL |
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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