ZM 447439
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.
ZM 447439是一种新型有效的和选择性的Aurora激酶抑制剂，Aurora激酶属于丝氨酸/苏氨酸激酶家族，对细胞分裂期间染色体的准确分离必不可少。体外实验中，ZM 447439抑制纯化的重组Aurora A和Aurora B蛋白的IC50值分别为110 nM和130 nM，从而抑制组蛋白H3丝氨酸10的磷酸化。ZM 447439特异性抑制Aurora激酶，对大多数其他蛋白激酶如CDK1/2/4、IKK1/2、 PLK1、CHK1、 cFLT2、KDR2、FAK 和 Zap-70基本无抑制作用（IC50 > 10 μM），而对MEK1、SRC 和LCK的IC50值分别为1.79 μM、1.03和0.88 μM[1-3]。
参考文献：
[1] 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.
[2] 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.
[3] 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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 513.59 |
| Cas No. | 331771-20-1 |
| Formula | C29H31N5O4 |
| Solubility | ≥25.7 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | N-[4-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]phenyl]benzamide |
| SDF | Download SDF |
| Canonical SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5 |
| 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。 |
| 激酶实验 [1]: | |
|
体外激酶实验 |
使用杆状病毒表达体系合成氨基末端被His6标记的Aurora A和Aurora B融合蛋白。使用Ni-NTA琼脂糖，通过亲和层析法纯化Aurora A，使用CM Sepharose Fast Flow，通过离子交换层析法纯化Aurora B。将1 ng 纯化后的重组蛋白酶加到反应中，反应体系含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多肽底物，10 μM ATP (Aurora A)，5 μM ATP (Aurora B)，和0.2 μCiγ-[33P]ATP（比活性 ≥ 2,500 Ci/mmol），然后将其置于室温下孵育60分钟。加入20%磷酸终止反应，使用P30硝化纤维过滤膜分离产物，采用BetaplateTM计数器测定33P摄入率。没有使用酶和化合物对照物来测定ZM 447439浓度，计算IC50值。 |
| 细胞实验 [2]: | |
|
细胞系 |
GEP-NET细胞系BON、QGP-1和MIP-101 |
|
制备方法 |
在DMSO中的溶解度大于10 mM。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 |
0 ~ 5 μM；72小时 |
|
实验结果 |
在BON、QGP-1和MIP-101细胞中，ZM 447439呈时间和剂量依赖性地抑制细胞生长，其IC50值分别为3 μM、0.9 μM和3 μM。 |
|
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. | |
| Description | ZM 447439是一种选择性Aurora B激酶抑制剂，IC50值为50 nM。 | |||||
| 靶点 | Aurora B | Aurora C | Aurora A | |||
| IC50 | 50nM | 250 nM | 1 μM | |||
质量控制和MSDS
- 批次:
化学结构
