KU-60019
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
KU-60019是一种选择性的ATM（Ataxia telangiectasia mutated）抑制剂，IC50值为6.3 nM。据报道，KU-60019对h-TERT永生化正常成纤维细胞而非A-T成纤维细胞具有放射增敏作用，表明KU-60019是一种特异性的ATM激酶放射增敏剂[1]。
据报道，在U87（p53野生型）和U1242（p53突变型）人脑胶质瘤细胞系中，KU-60019可以减少放射诱导的S473 AKT磷酸化，以剂量依赖的方式抑制细胞迁移和侵袭。除此之外，KU-60019还可以抑制U1242细胞的生长。然而，KU-60019对AKT的抑制并不会增强其放射增敏作用[1]。
参考文献：
[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.
- 1. Yaru Zhang, Marco Jost, et al. "Adaptive exchange sustains cullin–RING ubiquitin ligase networks and proper licensing of DNA replication." Proc Natl Acad Sci U S A. 2022 Sep 6;119(36):e2205608119. PMID: 36037385
- 2. Mathew J.K. Jones, Camille Gelot, et al. "Human DDK rescues stalled forks and counteracts checkpoint inhibition at unfired origins to complete DNA replication." Mol Cell. 2021 Feb 4;81(3):426-441.e8. PMID:33545059
- 3. Zheng K, Ma J, et al. "Sulforaphane Inhibits Autophagy and Induces Exosome-Mediated Paracrine Senescence via Regulating mTOR/TFE3." Mol Nutr Food Res. 2020;e1901231. PMID:32476238
- 4. Zhao K, Wang X, et al. "A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers." PLoS Biol. 2020;18(3):e3000666. PMID:32203529
- 5. Christine Wenz. "Cell confluence as crucial regulator of ROS-induced toxicity: Analysis of t-BuOOH-induced cell death in vitro." Gutenberg-Universität in Mainz. 2019.
- 6. 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
- 7. 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.
| Storage | Store at -20°C |
| M.Wt | 547.68 |
| Cas No. | 925701-49-1 |
| Formula | C30H33N3O5S |
| Synonyms | KU60019;KU 60019 |
| Solubility | ≥27.4 mg/mL in DMSO; insoluble in H2O; ≥51.2 mg/mL in EtOH |
| Chemical Name | 2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide |
| SDF | Download SDF |
| 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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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. |
|
| 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 | |||||
质量控制和MSDS
- 批次：
化学结构
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