ZM 447439

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Description: Inhibits Aurora kinase B
Chemical Name: N-[4-[[6-Methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl]amino]phenyl]benzamide
Purity: ≥98% (HPLC)
Citations (50)
Reviews (1)
Literature (2)

Biological Activity for ZM 447439

ZM 447439 is a 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.

Compound Libraries for ZM 447439

ZM 447439 is also offered as part of the Tocriscreen 2.0 Max, Tocriscreen Kinase Inhibitor Library and Tocriscreen Epigenetics Library. Find out more about compound libraries available from Tocris.

Technical Data for ZM 447439

M. Wt 513.59
Formula C29H31N5O4
Storage Store at -20°C
Purity ≥98% (HPLC)
CAS Number 331771-20-1
PubChem ID 9914412

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility Data for ZM 447439

Solvent Max Conc. mg/mL Max Conc. mM
DMSO 51.36 100

Preparing Stock Solutions for ZM 447439

The following data is based on the product molecular weight 513.59. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.95 mL 9.74 mL 19.47 mL
5 mM 0.39 mL 1.95 mL 3.89 mL
10 mM 0.19 mL 0.97 mL 1.95 mL
50 mM 0.04 mL 0.19 mL 0.39 mL

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Product Datasheets for ZM 447439

Certificate of Analysis / Product Datasheet
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References for ZM 447439

References are publications that support the biological activity of the product.

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

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

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

If you know of a relevant reference for ZM 447439, please let us know.

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Keywords: ZM 447439, ZM 447439 supplier, inhibitors, inhibits, Aurora, kinases, B, Mitosis, ZM447439, AstraZeneca, Kinases, 2458, Tocris Bioscience

50 Citations for ZM 447439

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

Sacristan et al (2018) Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nat Cell Biol 20 800 PMID: 29915359

Chen et al (2018) Atypical Cadherin Dachsous1b Interacts with Ttc28 and Aurora B to Control Microtubule Dynamics in Embryonic Cleavages. Dev Cell 45 376 PMID: 29738714

Wike et al (2016) Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis. Elife 5 e11402 PMID: 26878753

Wu et al (2014) Phosphorylation of myosin II-interacting guanine nucleotide exchange factor (MyoGEF) at threonine 544 by aurora B kinase promotes the binding of polo-like kinase 1 to MyoGEF. J Biol Chem 289 7142 PMID: 24482237

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

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

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

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

Balboula et al (2016) Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes. J Cell Sci 129 3648 PMID: 27562071

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

Wong et al (2018) Lipid accumulation facilitates mitotic slippage-induced adaptation to anti-mitotic drug treatment. Cell Death Discov 4 109 PMID: 30510774

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

Zhang et al (2017) Ska3 Phosphorylated by Cdk1 Binds Ndc80 and Recruits Ska to Kinetochores to Promote Mitotic Progression. Curr Biol 27 1477 PMID: 28479321

Haase et al (2017) Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment. Dev Cell 42 640 PMID: 28950102

Quartuccio et al (2017) Haspin inhibition reveals functional differences of interchromatid axis-localized AURKB and AURKC. Mol Biol Cell 28 2233 PMID: 28659416

Yakoubi et al (2017) Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I. Nat Commun 8 694 PMID: 28947820

Camlin et al (2017) Kif4 Is Essential for Mouse Oocyte Meiosis. PLoS One 12 e0170650 PMID: 28125646

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

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

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

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

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

Gulluni et al (2021) PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation. Science 374 PMID: 34882480

Pachis et al (2019) Interactions between N-terminal Modules in MPS1 Enable Spindle Checkpoint Silencing. Cell Rep 26 2101 PMID: 30784592

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

Kettenbach et al (2011) Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal 4 rs5 PMID: 21712546

Afonso et al (2019) Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk. Elife 8 PMID: 31424385

Shrestha (2017) Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells. Nat Commun 8 150 PMID: 28751710

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

Carmena et al (2012) The chromosomal passenger complex activates Polo kinase at centromeres. PLoS Biol 10 e1001250 PMID: 22291575

Lee et al (2012) In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase. PLoS One 7 e45836 PMID: 23029267

Meglicki et al (2012) Appearance and heterochromatin localization of HP1α in early mouse embryos depends on cytoplasmic clock and H3S10 phosphorylation. Cell Cycle 11 2189 PMID: 22622086

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

Littler et al (2019) Oncogenic MYC amplifies mitotic perturbations. Open Biol 9 190136 PMID: 31455158

Hindriksen et al (2017) Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells. PLoS One 12 e0179514 PMID: 28640891

Luciano et al (2013) Oocytes isolated from dairy cows with reduced ovarian reserve have a high frequency of aneuploidy and alterations in the localization of progesterone receptor membrane component 1 and aurora kinase B. Biol Reprod 88 58 PMID: 23325810

Rosa-Garrido et al (2012) A cell cycle role for the epigenetic factor CTCF-L/BORIS. PLoS One 7 e39371 PMID: 22724006

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

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

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

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

Lane et al (2010) The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. Reproduction 140 521 PMID: 20660090

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

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

Gascoigne and Taylor (2008) Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14 111 PMID: 18656424

Do you know of a great paper that uses ZM 447439 from Tocris? Please let us know.

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ZM447439 releases cells into mitosis.
By Valeria Marotta on 10/07/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: U2OS

The product was used to release the cells in mitosis after STLC clock

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Literature in this Area

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