ZM 447439
目录号 : GC14409
Selective inhibitor of Aurora B kinase
Cas No.:331771-20-1
Sample solution is provided at 25 µL, 10mM.
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ZM 447439 is a novel, potent and selective inhibitor of Aurora kinase, a family of serine/threonine kinases essential for accurate chromosome segregation during cell division, that inhibits the activity of purified recombinant Aurora A and Aurora B proteins in vitro with 50% inhibition concentration IC50 values of 110 nM and 130 nM respectively and hence inhibits phosphorylation of histone H3 on serine 10. Being specifically for Aurora kinases, ZM 447439 barely inhibits the majority of other protein kinases (IC50 > 10 μM), such as CDK1/2/4, IKK1/2, PLK1, CHK1, cFLT2, KDR2, FAK and Zap-70, except for MEK1, SRC and LCK (IC50 values of 1.79 μM, 1.03 and 0.88 μM respectively μM).
Reference
Li M, Jung A, Ganswindt U, Marini P, Friedl A, Daniel PT, Lauber K, Jendrossek V, Belka C. Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. Biochem Pharmacol. 2010 Jan 15;79(2):122-9. doi: 10.1016/j.bcp.2009.08.011. Epub 2009 Aug 15.
Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol. 2003 Apr 28;161(2):267-80.
Long ZJ, Xu J, Yan M, Zhang JG, Guan Z, Xu DZ, Wang XR, Yao J, Zheng FM, Chu GL, Cao JX, Zeng YX, Liu Q. ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensional culture. Cell Cycle. 2008 May 15;7(10):1473-9. Epub 2008 Mar 12.
| Kinase experiment [1]: | |
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In vitro kinase assays |
Recombinant Aurora A and B were expressed as NH2-terminal His6-tagged fusion proteins using a baculovirus expression system. Aurora A was purified by affinity chromatography using Ni-NTA agarose, and Aurora B was purified by ion exchange chromatography using CM Sepharose Fast Flow. 1 ng purified recombinant enzyme was added to a reaction cocktail containing 25 mM Tris-HCl, pH 7.5, 12.5 mM KCl, 2.5 mM NaF, 0.6 mM DTT, 6.25 mM MnCl2, 10 μM peptide substrate, 10 μM ATP for Aurora A or 5 μM ATP for Aurora B, and 0.2 μCi γ-[33P]ATP (specific activity ≥ 2,500 Ci/mmol), and was then incubated at RT for 60 mins. Reactions were stopped by addition of 20% phosphoric acid, and the products were captured on P30 nitrocellulose filters and assayed for incorporation of 33P with a BetaplateTM counter. No enzyme and no compound control values were used to determine the concentration of ZM 447439, which gave 50% inhibition of enzyme activity. |
| Cell experiment [2]: | |
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Cell lines |
GEP-NET cell lines BON, QGP-1 and MIP-101 |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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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Reaction Conditions |
0 ~ 5 μM; 72 hrs |
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Applications |
In BON, QGP-1 and MIP-101 cells, ZM 447439 time- and dose-dependently inhibited cell growth with IC50 values of 3 μM, 0.9 μM and 3 μM, respectively. |
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References: [1]. Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol. 2003 Apr 28;161(2):267-80. [2]. Georgieva I, Koychev D, Wang Y, Holstein J, Hopfenmüller W, Zeitz M, Grabowski P. ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines. Neuroendocrinology. 2010;91(2):121-30. | |
| Cas No. | 331771-20-1 | SDF | |
| 化学名 | N-[4-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]phenyl]benzamide | ||
| Canonical SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5 | ||
| 分子式 | C29H31N5O4 | 分子量 | 513.59 |
| 溶解度 | ≥ 25.7 mg/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 | 1.9471 mL | 9.7354 mL | 19.4708 mL |
| 5 mM | 0.3894 mL | 1.9471 mL | 3.8942 mL |
| 10 mM | 0.1947 mL | 0.9735 mL | 1.9471 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet