KU-60019
(Synonyms: KU60019;KU 60019) 目录号 : GC12054
A potent ATM kinase inhibitor
Cas No.:925701-46-8
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
U87 and U1242 cells |
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Preparation method |
The solubility of this compound in DMSO is > 27.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
3 μM; 1, 3 and 5 days |
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Applications |
In U87 cells, KU-60019 at 3 μM significantly inhibited cell migration and invasion by > 70% and ~ 60%, respectively. Similarly, KU-60019 also substantially inhibited migration and invasion of human glioma U1242 cells by > 50% and ~ 60%, respectively. |
| Animal experiment [2]: | |
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Animal models |
Athymic female mice implanted with U1242/luc-GFP cells |
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Dosage form |
KU-60019 (10 μM) delivered intratumorally at a rate of 0.5 μL/h by osmotic pump, for 14 days |
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Applications |
In athymic female mice implanted with U1242/luc-GFP cells, the combination of KU-60019 and radiation significantly inhibited tumor growth than radiation alone, which suggested that KU-60019 might radiosensitize U1242 gliomas. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. |
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| Cas No. | 925701-46-8 | SDF | |
| 别名 | KU60019;KU 60019 | ||
| 化学名 | 2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide | ||
| Canonical SMILES | CC1CN(CC(O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C=CC=C4C3)C5=CC(=O)C=C(O5)N6CCOCC6 | ||
| 分子式 | C30H33N3O5S | 分子量 | 547.68 |
| 溶解度 | ≥ 55.6mg/mL in DMSO with gentle warming, ≥ 27.4mg/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 | 1.8259 mL | 9.1294 mL | 18.2588 mL |
| 5 mM | 0.3652 mL | 1.8259 mL | 3.6518 mL |
| 10 mM | 0.1826 mL | 0.9129 mL | 1.8259 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet