Basic information Description Features In vitro Safety Supplier Related
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ZM 447439

Basic information Description Features In vitro Safety Supplier Related

ZM 447439 Basic information

Product Name:
ZM 447439
Synonyms:
  • N-[4-[[6-METHOXY-7-[3-(4-MORPHOLINYL)PROPOXY]-4-QUINAZOLINYL]AMINO]PHENYL]BENZAMIDE
  • ZM 447439
  • N-(4-((6-Methoxy-7-(3-Morpholinopropoxy)quinazolin-4-yl)aMino)phenyl)benzaMide
  • BenzaMide, N-[4-[[6-Methoxy-7-[3-(4-Morpholinyl)propoxy]-4-quinazolinyl]aMino]phenyl]-
  • ZM-447439;ZM447439
  • ZM 447439, >=98%
  • Aurora Kinase Inhibitor VI, ZM447439 - CAS 331771-20-1 - Calbiochem
  • CS-77
CAS:
331771-20-1
MF:
C29H31N5O4
MW:
513.59
Product Categories:
  • Inhibitor
  • Aromatics
  • Heterocycles
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
Mol File:
331771-20-1.mol
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ZM 447439 Chemical Properties

Melting point:
117-120°C
Boiling point:
639.7±55.0 °C(Predicted)
Density 
1.282±0.06 g/cm3(Predicted)
storage temp. 
Desiccate at RT
solubility 
Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 25 mg/ml).
form 
White solid
pka
13.01±0.70(Predicted)
color 
White
Stability:
Stable for 1 year from date of purchase? as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
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ZM 447439 Usage And Synthesis

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.

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. 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. 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. A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity to cisplatin

Description

The Aurora kinases have important roles in regulating mitosis and cytokinesis, with Aurora B involved in centromere function as part of the Chromosomal Passenger Complex, with survivin, INCENP, and borealin. ZM 447439 is a selective inhibitor of Aurora B kinase (IC50 = 50 nM), less potently inhibiting Aurora C and A (IC50 = 250 and 1,000 nM, respectively). It has no effect on several other kinases, including Cdk1, Cdk2, Cdk4, Plk1, CHK1, KDR2, and FAK (IC50 > 10 μM). ZM 447439 has been used to study the role of Aurora B in molecular events associated with mitosis and cytokinesis. Moreover, ZM 447439 selectively inhibits proliferating cells rather than non-dividing cells, suggesting its potential in cancer therapy.

Chemical Properties

Pale Yellow Solid

Uses

It is a potent and selective inhibitor of Aurora B kinase. Cells treated with ZM-447439 progress through interphase, enter mitosis and assemble bipolar spindles but chromosome alignment, segregation a nd cytokinesis all fail. It induces apoptosos in Hep2 cancer cells and in acute myeloid leukemia cell lines but its propensity to induce polyploidy does not inevitably result in apoptosis.

Uses

It is a potent and selective inhibitor of Aurora B kinase. Cells treated with ZM-447439 progress through interphase, enter mitosis and assemble bipolar spindles but chromosome alignment, segregation and cytokinesis all fail. It induces apoptosos in Hep2 cancer cells and in acute myeloid leukemia cell lines but its propensity to induce polyploidy does not inevitably result in apoptosis.

Definition

ChEBI: ZM447439 is a member of the class of quinazolines that is quinazoline which is substituted at positions 4, 6 and 7 by a (4-benzamidophenyl)nitrilo group, methoxy group and a 3-(morpholin-4-yl)propoxy group, respectively. It is an ATP-competitive inhibitor of Aurora A and Aurora B kinases with IC50 of 110 nM and 130 nM, respectively. It has a role as an Aurora kinase inhibitor, an antineoplastic agent and an apoptosis inducer. It is a member of benzamides, a member of quinazolines, an aromatic ether, a member of morpholines, a polyether, a secondary amino compound and a tertiary amino compound.

storage

room temperature (desiccate)

References

1) 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 2) Girdler et al. (2006) Validating Aurora B as an anti-cancer drug target; J. Cell Sci. 119 3664

ZM 447439Supplier

Shanghai EFE Biological Technology Co., Ltd. Gold
Tel
021-65675885 18964387627
Email
info@efebio.com
Products Intro
Product Name:ZM 447439
CAS:331771-20-1
Purity:99% Package:1mg;5mg;10mg
Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
Products Intro
Product Name:ZM447439
CAS:331771-20-1
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Email
jkinfo@jkchemical.com
Products Intro
Product Name:ZM 447439
CAS:331771-20-1
Package:100Mg,10Mg
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801 18930552037
Email
3bsc@sina.com
Products Intro
Product Name:ZM 447439;N-[4-[[6-Methoxy-7-[3-(4-Morpholinyl)propoxy]-4-quinazolinyl]aMino]phenyl]benzaMide
CAS:331771-20-1
Purity:99% HPLC Package:1Mg ; 5Mg;10Mg ;100Mg;250Mg ;500Mg ;1g;2.5g ;5g ;10g
Chembest Research Laboratories Limited
Tel
021-20908456
Email
sales@BioChemBest.com
Products Intro
Product Name:ZM 447439
CAS:331771-20-1
Remarks:C14364