产品说明书

AZD1080

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Chemical Structure| 612487-72-6 同义名 : -
CAS号 : 612487-72-6
货号 : A166126
分子式 : C19H18N4O2
纯度 : 99%+
分子量 : 334.372
MDL号 : MFCD12031593
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(59.81 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 3 mg/mL clear

PO 0.5% CMC-Na 26 mg/mL suspension

生物活性
靶点

  • GSK-3α

    GSK-3α, IC50:6.9 nM

  • GSK-3β

    GSK-3β, IC50:31 nM
描述 GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3a and b subunit, which plays a key role in many different biological processes including tumorigenesis, cell survival, and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/b-catenin signaling[1]. AZD1080 is thiazole-derived inhibitor of GSK-3 with Ki values of 6.9 nM and 31 nM for GSK-3a and b, respectively, with >37-fold selectivity over CDKs. AZD1080 can inhibit tau phosphorylation through GSK3 in concentration-dependent manner, with IC50 value of 324 nM, in 3T3 fibroblasts engineered to stably express 4-repeat human tau. Similar effect of reduction on tau phosphorylation can also be observed in hippocampus of rats with acute oral administration of AZD1080 at 10 μmol/kg. Oral administration of AZD1080 at 15 μmol/kg can reverse MK-801-induced impairments in mouse model of cognition, as well as rescue LTP deficits in mouse hippocampal slices[2]. Treatment with AZD1080 on 1 - 4 μM can suppress cell proliferation, migration and invasion, as well as increase cell apoptosis and modulate NF-kB, Cyclin D1, MMP9, and P21 expression in endometrial cancer cells[3].
作用机制 AZD1080 binds in the ATP pocket of GSK3b where the oxindole ring system forms hydrogen bonds to the back-bone of the ATP pocket[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.99mL

0.60mL

0.30mL

14.95mL

2.99mL

1.50mL

29.91mL

5.98mL

2.99mL
参考文献

[1]Domoto T, Pyko IV, et al. Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy. Cancer Sci. 2016 Oct;107(10):1363-1372.

[2]Georgievska B, Sandin 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.

[3]Chen S, Sun KX, et al. The role of glycogen synthase kinase-3β (GSK-3β) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker. Oncotarget. 2016 May 10;7(19):27538-51.