CGK733
(Synonyms: ATM/ATR Kinase Inhibitor) 目录号 : GC14526
An anticancer compound
Cas No.:905973-89-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Cells are seeded in 96-well plates at a predetermined optimal cell density to ensure exponential growth for duration of the assay. After a 24 h preincubation, growth medium is replaced with experimental medium containing the appropriate drug concentrations or 0.1% (v/v) vehicle control. After a 48 h incubation, cell proliferation is estimated using the sulforhodamine B colorimetric assay and expressed as the mean ± SE for six replicates as a percentage of vehicle control (taken as 100%). Experiments are performed independently at least three times. Statistical analyses are performed using a two-tailed Student's t test. P < 0.05 is considered to be statistically significant[2]. |
Animal experiment: | Four to six weeks old athymic CD-1 female mice are acclimatized for at least one week before use. The mice are injected sub-cutaneously with 2×106 D54-ATMR cells in each flank. Tumors are allowed to grow to the size of 100-150 mm3. Mice are injected intraperitoneally with vehicle control (DMSO), CGK-733, KU-55933 (25 mg/kg) or irradiated with 5 Gy to each flank. Bioluminescence is acquired on Xenogen IVIS Spectrum system after injecting 400 μg/100 μL of D-luciferin at baseline (-3h) as well as 1, 4, and 8 hours after drug administration[3]. |
References: [1]. Wang H, et al. CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2012 May 25;422(1):103-8. | |
CGK733 is an inhibitor of kinase ATM and ATR with IC50 value of ~200 nM [1].
Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase which plays pivotal role in DNA repair and cell cycle checkpoints. And when in hypoxia circumstance, loss of ATM-related (ATR) kinase induces the decreasing of HIF-1 DNA binding, which consequently affects GLUT-1 and CAIX expression in the protein level. The components of ATM and ATR regulated signaling pathways which enhances cellular sensitivity to chemo- and radiotherapy thus provide attractive pharmacological targets [2, 3].
CGK733 selectively inhibited ATM and ATR kinase activities and blocked their checkpoint signaling pathways. Treated HEK-293 cells with GSK733 would increase the sensitivity of cells to radiotherapy [1]. When tested with HBV-positive HCC cell line HepG2.2.15, CGK733 treatment significantly increased the cells sensitivity to taxol via inducing the formation of multinucleated cells [2]. Treated with CGK733, senescent breast, lung, and colon carcinoma cells were induced to undergo cell death [4]. CGK733 treated tumor cells could enhance the sensitivity to radio therapy via inhibiting DNA repair and cell cycle checkpoints of tumor cells [5]. In MCF-7 breast cancer cells, CGK733 treatment induced detectable decline levels of cyclin D1 protein and reduced phosphorylated and total retinoblastoma protein (RB) which inhibited cell proliferation [3].
References:
[1]. Williams, T.M., et al., Molecular imaging of the ATM kinase activity. Int J Radiat Oncol Biol Phys, 2013. 86(5): p. 969-77.
[2]. Wang, H., et al., CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells. Biochem Biophys Res Commun, 2012. 422(1): p. 103-8.
[3]. Alao, J.P. and P. Sunnerhagen, The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Radiat Oncol, 2009. 4(51): p. 4-51.
[4]. Crescenzi, E., et al., Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy. Clin Cancer Res, 2008. 14(6): p. 1877-87.
[5]. Kuroda, S., Y. Urata, and T. Fujiwara, Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: promising targets for radiosensitization. Acta Med Okayama, 2012. 66(2): p. 83-92.
| Cas No. | 905973-89-9 | SDF | |
| 别名 | ATM/ATR Kinase Inhibitor | ||
| 化学名 | 2,2-diphenyl-N-[2,2,2-trichloro-1-[(4-fluoro-3-nitrophenyl)carbamothioylamino]ethyl]acetamide | ||
| Canonical SMILES | C1=CC=C(C=C1)C(C2=CC=CC=C2)C(=O)NC(C(Cl)(Cl)Cl)NC(=S)NC3=CC(=C(C=C3)F)[N+](=O)[O-] | ||
| 分子式 | C23H18Cl3FN4O3S | 分子量 | 555.84 |
| 溶解度 | ≥ 27.8mg/mL in DMSO, ≥ 5.55mg/mL in EtOH with ultrasonic and warming | 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 | 1.7991 mL | 8.9954 mL | 17.9908 mL |
| 5 mM | 0.3598 mL | 1.7991 mL | 3.5982 mL |
| 10 mM | 0.1799 mL | 0.8995 mL | 1.7991 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。