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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.
Sold with the permission of AstraZeneca UK Ltd.
|Storage||Store at -20°C|
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.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
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.
|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|
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
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Keywords: ZM 447439, ZM 447439 supplier, inhibitors, inhibits, Aurora, kinases, B, Mitosis, ZM447439, AstraZeneca, Kinases, 2458, Tocris Bioscience
49 Citations for ZM 447439
Citations are publications that use Tocris products. Selected citations for ZM 447439 include:
Littler et al (2019) Oncogenic MYC amplifies mitotic perturbations. Open Biol 9 190136 PMID: 31455158
Afonso et al (2019) Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk. Elife 8 PMID: 31424385
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
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
Pachis et al (2019) Interactions between N-terminal Modules in MPS1 Enable Spindle Checkpoint Silencing. Cell Rep 26 2101 PMID: 30784592
Hindriksen et al (2017) Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells. PLoS One 12 e0179514 PMID: 28640891
Ferreira et al (2013) Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J Cell Biol 201 709 PMID: 23712260
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
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
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
Samoshkin et al (2009) Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation. PLoS One 4 e6831 PMID: 19714251
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
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
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
Kim and Yu (2015) Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human mitotic kinetochores. J Cell Biol 208 181 PMID: 25601404
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
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
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
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
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
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
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
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
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
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
Wang et al (2012) Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol 199 251 PMID: 23071152
Vázquez-Novelle and Petronczki (2010) Relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase. Curr Biol 20 1402 PMID: 20619651
Bastos and Barr (2010) Plk1 negatively regulates Cep55 recruitment to the midbody to ensure orderly abscission. J Cell Biol 191 751 PMID: 21079244
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
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
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Cell Cycle & DNA Damage Repair Poster
In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.