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KU-60019

现货
Catalog No.
A8336
ATM激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
10mg
¥ 980.00
现货
50mg
¥ 3,000.00
现货
200mg
¥ 9,000.00
现货

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Background

KU-60019 is a selective inhibitor of the Ataxia telangiectasia (A-T) mutated (ATM) protein with an IC50 value of 6.3 nM. In literature report, KU-60019 radiosensitizes h-TERT-immortalized normal fibroblasts but not A-T fibroblasts, suggesting it is a specific ATM kinase radiosensitizer [1].

KU-60019 can reduce radiation-induced S473 AKT phosphorylation in human glioma cell lines that are p53 wild type (U87) and p53 mutant (U1242). However, the suppression of AKT does not enhance radiosensitization of KU-60019 [1].

KU-60019 has been reported to inhibit cell migration and invasion in human glioma cells U87 and U1242 in a dose-dependent manner. Besides, KU-60019, to some extent, has also been shown to suppress the growth of U1242 cells [1].

References:
[1] Golding SE1, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ,Povirk LF, van Meter T, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902.

文献引用

1. Caster JM, Yu SK, et al. "Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy."Nanomedicine. 2017 Mar 11. pii: S1549-9634(17)30044-8. PMID:28300658
2. Mignon Albertha van Vuuren. "The role of Atm in the regulation of cardiomyocyte glucose utilization under normal and insulin resistant conditions." Stellenbosch University.March 2016.

Chemical Properties

StorageStore at -20°C
M.Wt547.68
Cas No.925701-49-1
FormulaC30H33N3O5S
SynonymsKU60019;KU 60019
Solubility≥55.6mg/mL in DMSO with gentle warming, ≥27.4mg/mL in DMSO
Chemical Name2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide
SDFDownload SDF
Canonical SMILESCC1CN(CC(O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C=CC=C4C3)C5=CC(=O)C=C(O5)N6CCOCC6
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

U87和U1242细胞

制备方法

在DMSO中的溶解度大于27.4 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

3 μM;1、3和5天

实验结果

在U87细胞中,3μM KU-60019显著抑制细胞迁移(> 70%)与侵袭(~ 60%)。同样地,KU-60019也显著抑制人胶质瘤U1242细胞的迁移(> 50%)与侵袭(~ 60%)。

动物实验 [2]:

动物模型

植入U1242/luc-GFP细胞的去胸腺雌性小鼠

给药剂量

在肿瘤内使用渗透泵以0.5 μL/h的速度注射KU-60019 (10 μM),持续14天

实验结果

在植入U1242/luc-GFP细胞的去胸腺雌性小鼠中,相对于放疗,KU-60019和放疗联合使用显著抑制肿瘤生长。因此,KU-60019可能增加U1242神经胶质瘤对放疗的敏感性。

其它注意事项

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]. Golding SE1, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ,Povirk LF, van Meter T, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902.

[2]. Biddlestone-Thorpe L, Sajjad M, Rosenberg E, Beckta JM, Valerie NC, Tokarz M, Adams BR, Wagner AF, Khalil A, Gilfor D, Golding SE, Deb S, Temesi DG, Lau A, O'Connor MJ, Choe KS, Parada LF, Lim SK, Mukhopadhyay ND, Valerie K. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res. 2013 Jun 15;19(12):3189-200.

生物活性

描述 KU-60019是KU-55933的类似物,在非细胞试验中作用于ATM,IC50值为6.3 nM,比对DNA-PK和ATR的选择性分别高270和1600倍。
靶点 ATM          
IC50 6.3 nM          

质量控制

化学结构

KU-60019

相关生物数据

KU-60019

相关生物数据

KU-60019

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KU-60019

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KU-60019