Home Cell Cycle Aurora Kinase inhibitor ZM 447439 For research use only.

ZM 447439

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

ZM 447439 Chemical Structure

ZM 447439 Chemical Structure

CAS No. 331771-20-1

Purity & Quality Control

ZM 447439 Related Products

Signaling Pathway

Aurora Kinase Signaling Pathways

Aurora Kinase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human EoL-1-cell Growth inhibition assay Inhibition of human EoL-1-cell cell growth in a cell viability assay, IC50=0.18678 μM SANGER
MCF7 cell Proliferation assay Antiproliferative activity against MCF7 cell line, IC50=0.198 μM 16337122
human P12-ICHIKAWA cell Growth inhibition assay Inhibition of human P12-ICHIKAWA cell growth in a cell viability assay, IC50=0.22441 μM SANGER
human KARPAS-45 cell Growth inhibition assay Inhibition of human KARPAS-45 cell growth in a cell viability assay, IC50=0.38128 μM SANGER
human ES3 cell Growth inhibition assay Inhibition of human ES3 cell growth in a cell viability assay, IC50=0.4732 μM SANGER
human ES8 cell Growth inhibition assay Inhibition of human ES8 cell growth in a cell viability assay, IC50=0.49806 μM SANGER
human TE-11 cell Growth inhibition assay Inhibition of human TE-11 cell growth in a cell viability assay, IC50=0.53703 μM SANGER
human RS4-11 cell Growth inhibition assay Inhibition of human RS4-11 cell growth in a cell viability assay, IC50=0.5544 μM SANGER
human MOLT-16 cell Growth inhibition assay Inhibition of human MOLT-16 cell growth in a cell viability assay, IC50=0.60961 μM SANGER
human RKO cell Growth inhibition assay Inhibition of human RKO cell growth in a cell viability assay, IC50=0.70656 μM SANGER
human MV-4-11 cell Growth inhibition assay Inhibition of human MV-4-11 cell growth in a cell viability assay, IC50=0.7963 μM SANGER
human SW954 cell Growth inhibition assay Inhibition of human SW954 cell growth in a cell viability assay, IC50=0.83635 μM SANGER
human BE-13 cell Growth inhibition assay Inhibition of human BE-13 cell growth in a cell viability assay, IC50=0.84418 μM SANGER
human MOLT-4 cell Growth inhibition assay Inhibition of human MOLT-4 cell growth in a cell viability assay, IC50=0.89978 μM SANGER
human NBsusSR cell Growth inhibition assay Inhibition of human NBsusSR cell growth in a cell viability assay, IC50=0.91387 μM SANGER
human H9 cell Growth inhibition assay Inhibition of human H9 cell growth in a cell viability assay, IC50=0.92979 μM SANGER
human A172 cell Growth inhibition assay Inhibition of human A172 cell growth in a cell viability assay, IC50=0.98411 μM SANGER
human ES5 cell Growth inhibition assay Inhibition of human ES5 cell growth in a cell viability assay, IC50=1.00248 μM SANGER
human SBC-1 cell Growth inhibition assay Inhibition of human SBC-1 cell growth in a cell viability assay, IC50=1.03928 μM SANGER
human NCI-H209 cell Growth inhibition assay Inhibition of human NCI-H209 cell growth in a cell viability assay, IC50=1.16602 μM SANGER
human NKM-1 cell Growth inhibition assay Inhibition of human NKM-1 cell growth in a cell viability assay, IC50=1.16798 μM SANGER
human NCI-H720 cell Growth inhibition assay Inhibition of human NCI-H720 cell growth in a cell viability assay, IC50=1.20627 μM SANGER
human KE-37 cell Growth inhibition assay Inhibition of human KE-37 cell growth in a cell viability assay, IC50=1.21388 μM SANGER
human SW48 cell Growth inhibition assay Inhibition of human SW48 cell growth in a cell viability assay, IC50=1.23155 μM SANGER
human IST-SL1 cell Growth inhibition assay Inhibition of human IST-SL1 cell growth in a cell viability assay, IC50=1.31727 μM SANGER
human SK-NEP-1 cell Growth inhibition assay Inhibition of human SK-NEP-1 cell growth in a cell viability assay, IC50=1.36498 μM SANGER
human NOMO-1 cell Growth inhibition assay Inhibition of human NOMO-1 cell growth in a cell viability assay, IC50=1.36725 μM SANGER
human DOHH-2 cell Growth inhibition assay Inhibition of human DOHH-2 cell growth in a cell viability assay, IC50=1.40276 μM SANGER
human ABC-1 cell Growth inhibition assay Inhibition of human ABC-1 cell growth in a cell viability assay, IC50=1.40352 μM SANGER
human Ramos-2G6-4C10 cell Growth inhibition assay Inhibition of human Ramos-2G6-4C10 cell growth in a cell viability assay, IC50=1.40605 μM SANGER
human EM-2 cell Growth inhibition assay Inhibition of human EM-2 cell growth in a cell viability assay, IC50=1.41721 μM SANGER
human NB14 cell Growth inhibition assay Inhibition of human NB14 cell growth in a cell viability assay, IC50=1.55621 μM SANGER
human MOLT-13 cell Growth inhibition assay Inhibition of human MOLT-13 cell growth in a cell viability assay, IC50=1.56706 μM SANGER
human ECC10 cell Growth inhibition assay Inhibition of human ECC10 cell growth in a cell viability assay, IC50=1.63353 μM SANGER
human LK-2 cell Growth inhibition assay Inhibition of human LK-2 cell growth in a cell viability assay, IC50=1.64594 μM SANGER
human CTB-1 cell Growth inhibition assay Inhibition of human CTB-1 cell growth in a cell viability assay, IC50=1.67082 μM SANGER
human NCI-H1581 cell Growth inhibition assay Inhibition of human NCI-H1581 cell growth in a cell viability assay, IC50=1.6755 μM SANGER
human COLO-800 cell Growth inhibition assay Inhibition of human COLO-800 cell growth in a cell viability assay, IC50=1.70382 μM SANGER
human NB7 cell Growth inhibition assay Inhibition of human NB7 cell growth in a cell viability assay, IC50=1.75297 μM SANGER
human LAMA-84 cell Growth inhibition assay Inhibition of human LAMA-84 cell growth in a cell viability assay, IC50=1.7552 μM SANGER
human HCT-116 cells Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=1.80908 μM SANGER
SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=1.8153 μM SANGER
human H4 cell Growth inhibition assay Inhibition of human H4 cell growth in a cell viability assay, IC50=1.81578 μM SANGER
human CAL-51 cell Growth inhibition assay Inhibition of human CAL-51 cell growth in a cell viability assay, IC50=1.83845 μM SANGER
human LoVo cells Proliferation assay 72 h Antiproliferative activity against human LoVo cells after 72 hrs by MTT-based WST8 reagent assay, IC50=1.9 μM 25270403
human HN cell Growth inhibition assay Inhibition of human HN cell growth in a cell viability assay, IC50=1.9251 μM SANGER
human L-363 cell Growth inhibition assay Inhibition of human L-363 cell growth in a cell viability assay, IC50=1.9512 μM SANGER
human NCI-H747 cell Growth inhibition assay Inhibition of human NCI-H747 cell growth in a cell viability assay, IC50=2.03353 μM SANGER
human A498 cell Growth inhibition assay Inhibition of human A498 cell growth in a cell viability assay, IC50=2.3669 μM SANGER
Click to View More Cell Line Experimental Data

Biological Activity

Description ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.
Features An Aurora selective ATP-competitive inhibitor.
Targets
Aurora A [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 LCK [1]
(Cell-free assay)		 Src [1]
(Cell-free assay)		 MEK1 [1]
(Cell-free assay)
110 nM 130 nM 880 nM 1.03 μM 1.79 μM
In vitro
In vitro

In vitro, ZM-447439 selectively inhibits recombinant human Aurora A and B with IC50 values of 110 and 130 nM, respectively, while other protein kinases of diverse structural types including the mitotic kinases CDK1 and PLK1 are inhibited with IC50 values >10 μM. [1] Aurora kinase inhibitor, ZM-447439 time- and dose-dependently inhibits the growth of all three cell lines with IC50 values of 3 μM (BON), 0.9 μM (QGP-1) and 3 μM (MIP-101) after 72 hours of continuous exposure. In addition, ZM-447439 potently induces cell apoptosis by promoting DNA fragmentation and caspase 3 and 7 activation, and arrests GEP-NET cells in the G0 /G1and G2/M phase of the cell cycle. [2] In mouse embryo, inhibition of Aurora kinase activity by ZM-447439 results in abnormalities during mitosis by regulating the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase with different perturbations in each embryonic cycle. [3] A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity. [4]
Kinase Assay In vitro kinase assays
Recombinant Aurora A and B are expressed as NH2-terminal His6-tagged fusion proteins using a baculovirus expression system. Aurora A is purified by affinity chromatography using Ni-NTA agarose, and Aurora B is purified by ion exchange chromatography using CM Sepharose Fast Flow. 1 ng purified recombinant enzyme is 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 for Aurora A or 5 μM ATP for Aurora B, and 0.2 μCi γ-[33P]ATP (specific activity ≥2,500 Ci/mmol), and is then incubated at RT for 60 minutes. Reactions are stopped by addition of 20% phosphoric acid, and the products are captured on P30 nitrocellulose filters and assayed for incorporation of 33P with a BetaplateTM counter. No enzyme and no compound control values are used to determine the concentration of ZM447439, which gave 50% inhibition of enzyme activity. Further details are available on request from Nicholas Keen.
Cell Research Cell lines BON, QGP-1 and MIP-101 cells
Concentrations 0-5 μM
Incubation Time 72 hours
Method

Cell number is evaluated by crystal violet staining. In brief, cells in 96-well plates are fixed with 1% glutaraldehyde. Then cells are stained with 0.1% crystal violet. The unbound dye is removed by washing with water. Bound crystal violet is solubilized with 0.2% Triton X-100. Light extinction which increases linearly with the cell number is analyzed at 570 nm using an ELISA reader.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p53 / p21 / p-p38 / p38 pHistone H3 / CEM BubR1 / MAD2 / Cyclin B1 23759594
Immunofluorescence p21 p53 Aurora B / Survivin 23759594

Chemical Information & Solubility

Molecular Weight 513.59 Formula

C29H31N5O4
CAS No. 331771-20-1 SDF Download ZM 447439 SDF
Smiles COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 103 mg/mL ( (200.54 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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