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AZD1080

现货
Catalog No.
B1536
GSK3β抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,420.00
现货
5mg
¥ 1,900.00
现货
10mg
¥ 3,000.00
现货
25mg
¥ 6,200.00
现货
50mg
¥ 8,500.00
现货
100mg
¥ 13,300.00
现货

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Background

AZD1080 is a novel, potent and selective inhibitor of Glycogen synthase kinase-3β (GSK3β) with the Ki values of 6.9 nM and 31 nM, respectively [1].

AZD1080 has been reported to inhibit GSK3β by binding within the ATP pocket by means of the high resolution X-ray crystal structure. In addition, AZD1080 has been noted to suppression recombinant human GSK3α and GSK3β with the Ki values of 6.9 nM and 31 nM, respectively. AZD1080 has also shown the selectivity against other kinases with the Ki values of 1150nM, 429nM,1980nM and >10μM for cdk2, cdk5, cdk2 and Erk2, respectively. Furthermore, AZD1080 has been revealed to concentration-dependently inhibit tau phosphorylation with the IC50 value of 324nM in 3T3 cell lines. Besides, AZD1080 has exhibited the good oral bioavailability the high blood – brain barrier permeability values of 8 ×10-3cm/min in rat [1].

References:
[1] Georgievska B1, Sandin J, Doherty J, Mörtberg A, Neelissen J, Andersson A, Gruber S, Nilsson Y, Schött P, Arvidsson PI, Hellberg S, Osswald G, Berg S, Fälting J, Bhat RV. AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem. 2013 May;125(3):446-56.

文献引用

1. Croft CL, Cruz PE, et al. "rAAV-based brain slice culture models of Alzheimer's and Parkinson's disease inclusion pathologies." J Exp Med. 2019 Mar 4;216(3):539-555. PMID:30770411

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt334.37
Cas No.612487-72-6
FormulaC19H18N4O2
Solubility≥16.7mg/mL in DMSO
Chemical Name3-[5-(morpholin-4-ylmethyl)-1H-pyridin-2-ylidene]-2-oxo-1H-indole-5-carbonitrile
SDFDownload SDF
Canonical SMILESC1COCCN1CC2=CNC(=C3C4=C(C=CC(=C4)C#N)NC3=O)C=C2
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

稳定表达4重复人tau蛋白的3T3成纤维细胞

制备方法

溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

37℃

实验结果

AZD1080以浓度依赖性方式抑制人tau蛋白的磷酸化,IC50为324 nM。非选择性参考GSK3抑制剂LiCl的IC50为1.5 mM,表明AZD1080比LiCl的效果高几个数量级。

动物实验: [1]

动物模型

11-12天的雄性和雌性Sprague-Dawley大鼠

给药剂量

AZD1080 (3或10 lmol/kg),口服,6 mL/kg

实验结果

在海马中,AZD1080给药后6小时抑制tau磷酸化的最大值为38 ± 2%和48 ± 2%,表明大脑中AZD1080以时间和剂量依赖性方式有效抑制tau 蛋白P-Thr231表位磷酸化。此外,AZD1080逆转小鼠的认知缺陷,并挽救功能障碍突触。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Georgievska B, Sandin J, Doherty J et al. AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem. 2013 May;125(3):446-56.

生物活性

描述 AZD1080是一个选择性的、可口服的和脑通透性的GSK3抑制剂,作用于人的GSK3α和GSK3β,Ki值分别为6.9 nM和31 nM。
靶点 GSK-3α GSK-3β        
IC50 6.9 nM (Ki) 31 nM (Ki)        

质量控制

化学结构

AZD1080

相关生物数据

AZD1080