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AR-A014418

现货
Catalog No.
A3184
GSK3β抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 640.00
现货
10mg
¥ 680.00
现货
50mg
¥ 1,890.00
现货

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Background

IC50: 104 ± 27 nM

Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer’s disease (AD). AR-A014418 is a selective GSK-3 inhibitor.

In vitro: ARA014418 acted as an ATP-competitive manner and did not significantly inhibit cdk2 or cdk5 or 26 other kinases demonstrating high specificity for GSK3. AR-A014418 inhibited tau phosphorylation at a GSK3-specific site (Ser-396) in cells stably expressing human four-repeat tau protein [1].

In vivo: ARA014418 induced behavioural changes that were consistent with the effects of antidepressant drugs. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, which was a well-established model for antidepressant efficacy. Moreover, the specificity of this effect was supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity [2].

Clinical trial: currently no clinical data were available.

References:
[1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Rades ter AC, Jerning E, Markgren PO, Borgeg rd T, Nyl f M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J.  Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45.
[2] Gould TD, Einat H, Bhat R, Manji HK.  AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90.

文献引用

1. Chen YJ, Huang CH, et al. "The suppressive effect of arsenic trioxide on TET2-FOXP3-Lyn-Akt axis-modulated MCL1 expression induces apoptosis in human leukemia cells." Toxicol Appl Pharmacol. 2018 Nov 1;358:43-55. PMID:30213730
2. Lee YC, Chen YJ, et al. "Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1. Apoptosis." 2016 Oct 19. PMID:27757735

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt308.31
Cas No.487021-52-3
FormulaC12H12N4O4S
SynonymsAR-AO 14418;AR 0133418;AR 014418;GSK 3β inhibitor
Solubility≥15.4 mg/mL in DMSO, <2.19 mg/mL in EtOH, <2.7 mg/mL in H2O
Chemical Name1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)urea
SDFDownload SDF
Canonical SMILESCOC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-]
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

酶学实验 [1]:

激酶检测

酶学竞争性试验中考察了10个抑制剂浓度,复孔。2 微摩尔生物素化生肽底物加入到包含6毫单位的人重组GSK3酶、12毫摩尔MOPS,pH 7.0、0.3毫摩尔EDTA、0.01% β-巯基乙醇, 0.004% Brij 35, 0.5% 甘油, and 0.5 微克 小牛血清白蛋白的缓冲液中。通过加入25微升含有0.04 μCi of [-33P]ATP已经未标记的ATP的50毫摩尔Mg(Ac)2溶液起始反应。室温孵育29分钟后,加入25微升含有5毫摩尔EDTA、50微摩尔ATP、0.1% Triton X-100以及0.25毫克链霉亲和素包被的SPA终止反应。

细胞实验 [1]:

细胞系

稳定表达4-重复tau蛋白的3T3成纤维细胞

溶解方法

在DMSO中的溶解度> 15.4 mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

100 nM到50 μM;孵育24小时

应用

在稳定表达4-重复tau蛋白的人3T3成纤维细胞中,AR-A014418能够抑制tau蛋白在GSK3的特定位点磷酸化。AR-A014418也能通过抑制磷脂酰肌醇3激酶/蛋白激酶B通路防止N2A成神经细胞瘤细胞死亡。

动物实验 [2]:

动物模型

雄性SD大鼠

剂量

30 μmol/kg,腹腔注射

应用

亚急性腹膜内注射AR-A014418能够减少暴露于强制游泳试验的大鼠的静止时间,这是一种成熟的抗抑郁药功效模型。 此外,研究表明AR-A014418能降低自发以及安非他明诱导的大鼠活性,该发现也支持了该效应的特异性。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Radester AC, Jerning E, Markgren PO, Borgegrd T, Nylf M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45.

[2] Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90.

生物活性

描述 AR-A014418是一种ATP竞争性的和选择性的GSK3β抑制剂,IC50和Ki值分别为104 nM和38 nM。
靶点 GSK-3          
IC50 104 +/- 27 nM          

质量控制

化学结构

AR-A014418

相关生物数据

AR-A014418

相关生物数据

AR-A014418