ZM 447439

Cat. No. 2458

ZM 447439 C29H31N5O4 [331771-20-1]

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Chemical Name: N-[4-[[6-Methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl]amino]phenyl]benzamide

Biological Activity

Novel, selective ATP-competitive inhibitor of Aurora B kinase in vitro (IC50 values are 50, 250 and 1000 nM for Aurora B, C and A kinases respectively). Selective over a range of other kinases including cdk1 and PLK1 (IC50 > 10 μM). Inhibits cell division and displays selective toxicity towards proliferating tumor cells versus non-dividing cells.

Licensing Information

Sold with the permission of AstraZeneca UK Ltd.

Technical Data

M.Wt:
513.59
Formula:
C29H31N5O4
Solubility:
Soluble to 100 mM in DMSO
Purity:
>98 %
Storage:
Store at -20°C
CAS No:
331771-20-1

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
All Tocris products are intended for laboratory research use only.

Certificate of Analysis / Product Datasheet / Safety Data Sheet

Certificate of Analysis / Product Datasheet
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Girdler et al (2006) Validating Aurora B as an anti-cancer drug target. J.Cell Sci. 119 3664. PMID: 16912073.

Jung et al (2006) Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors. J.Med.Chem. 49 955. PMID: 16451062.

Ditchfield et al (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J.Cell Biol. 161 267. PMID: 12719470.

If you know of a relevant reference for this product please let us know.

Citations are publications that use Tocris products. Selected citations for ZM 447439 include:

Kim and Yu (2015) Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human mitotic kinetochores. J Cell Biol 208 181. PMID: 25601404.

Platani et al (2015) Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes. J Cell Biol 210 45. PMID: 26124292.

Tauchman et al (2015) Stable kinetochore-microtubule attachment is sufficient to silence the spindle assembly checkpoint in human cells. J Cell Sci 6 10036. PMID: 26620470.

Balboula and Schindler (2014) Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes. PLoS Genet 10 e1004194. PMID: 24586209.

Mäki-Jouppila et al (2014) Centmitor-1, a novel acridinyl-acetohydrazide, possesses similar molecular interaction field and antimitotic cellular phenotype as rigosertib, on 01910.Na. Nat Commun 13 1054. PMID: 24748653.

Ferreira et al (2013) Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J Cell Biol 201 709. PMID: 23712260.

Floyd et al (2013) Spatiotemporal organization of Aurora-B by APC/CCdh1 after mitosis coordinates cell spreading through FHOD1. Cell Cycle 126 2845. PMID: 23613471.

Wang et al (2012) Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol 199 251. PMID: 23071152.

Foley et al (2011) Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nat Cell Biol 13 1265. PMID: 21874008.

Kasuboski et al (2011) Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores. Mol Biol Cell 22 3318. PMID: 21775627.

Tardáguila et al (2011) Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes. Mol Endocrinol 25 385. PMID: 21239609.

Yuan et al (2011) Polo-box domain inhibitor poloxin activates the spindle assembly checkpoint and inhibits tumor growth in vivo. Am J Pathol 179 2091. PMID: 21839059.

Bassett et al (2010) Epigenetic centromere specification directs aurora B accumulation but is insufficient to efficiently correct mitotic errors. Mol Cancer Ther 190 177. PMID: 20643881.

Bastos and Barr (2010) Plk1 negatively regulates Cep55 recruitment to the midbody to ensure orderly abscission. J Cell Biol 191 751. PMID: 21079244.

Jelluma et al (2010) Release of Mps1 from kinetochores is crucial for timely anaphase onset. Cell Cycle 191 281. PMID: 20937696.

Manchado et al (2010) Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase. Cancer Cell 18 641. PMID: 21156286.

Pal et al (2010) Role of a novel coiled-coil domain-containing protein CCDC69 in regulating central spindle assembly. J Am Soc Nephrol 9 4117. PMID: 20962590.

Vázquez-Novelle and Petronczki (2010) Relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase. Curr Biol 20 1402. PMID: 20619651.

Xu et al (2010) VHL inactivation induces HEF1 and Aurora kinase A. J Cell Biol 21 2041. PMID: 20864688.

Platani et al (2009) The Nup107-160 nucleoporin complex promotes mitotic events via control of the localization state of the chromosome passenger complex. Mol Biol Cell 20 5260. PMID: 19864462.

Samoshkin et al (2009) Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation. PLoS One 4 e6831. PMID: 19714251.

Scutt et al (2009) Discovery and exploitation of inhibitor-resistant aurora and polo kinase mutants for the analysis of mitotic networks. J Biol Chem 284 15880. PMID: 19359241.

Ganguly et al (2008) Cell cycle dependent degradation of MCAK: evidence against a role in anaphase chromosome movement. Toxins (Basel) 7 3187. PMID: 18843200.

Slawson et al (2008) A mitotic GlcNAcylation/phosphorylation signaling complex alters the posttranslational state of the cytoskeletal protein vimentin. Mol Biol Cell 19 4130. PMID: 18653473.

Vischioni et al (2006) Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients. Mol Cancer Ther 5 2905. PMID: 17121938.

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Keywords: ZM 447439, supplier, inhibitors, inhibits, Aurora, kinases, B, Mitosis, ZM447439, AstraZeneca, Tocris Bioscience, Aurora Kinase Inhibitor products

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