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ZM 447439Aurora Kinase inhibitor,potent and selective

ZM 447439

Catalog No. A4113
Size Price Stock Qty
10mM (in 1mL DMSO) $70.00 In stock
5mg $40.00 In stock
10mg $75.00 In stock
25mg $160.00 In stock
50mg $260.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

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Chemical structure

ZM 447439

Biological Activity

Description ZM 447439 is a selective inhibitor of Aurora B kinase with IC50 value of 50nM.
Targets Aurora B Aurora C Aurora A      
IC50 50nM 250 nM 1 μM      

Protocol

Kinase experiment [1]:

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]:

Cell lines

GEP-NET cell lines BON, QGP-1 and MIP-101

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.

Reacting condition

0 ~ 5 μM; 72 hrs

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.

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.

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Chemical Properties

Cas No. 331771-20-1 SDF Download SDF
Chemical Name 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
Formula C29H31N5O4 M.Wt 513.59
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

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.