AZD2858
目录号 : GC14736
A GSK3β inhibitor
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 | |
| 化学名 | 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 | ||
| 分子式 | C21H23N7O3S | 分子量 | 453.52 |
| 溶解度 | ≥ 11.35mg/mL in DMSO | 储存条件 | Store at -20° C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet