331771-20-1 Usage
Description
ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B kinases, with IC50 values of 110 nM and 130 nM, respectively. It is a pale yellow solid that is more than 8-fold selective for Aurora A/B than MEK1, Src, and Lck, and has little effect against CDK1/2/4, Plk1, Chk1, and other kinases. The Aurora kinases play crucial roles in regulating mitosis and cytokinesis, with Aurora B being a part of the Chromosomal Passenger Complex involved in centromere function.
Uses
Used in Cancer Therapy:
ZM 447439 is used as an inhibitor of Aurora B kinase for cancer therapy. It is particularly effective in inducing apoptosis in Hep2 cancer cells and acute myeloid leukemia cell lines. However, its propensity to induce polyploidy does not always result in apoptosis.
Used in Anticancer Applications:
ZM 447439 is used as an anticancer agent, selectively inhibiting proliferating cells rather than non-dividing cells, which suggests its potential in cancer therapy.
Used in Research:
ZM 447439 is used as a research tool to study the role of Aurora B in molecular events associated with mitosis and cytokinesis. Its selective inhibition of Aurora B kinase allows for a better understanding of the complex processes involved in cell division.
Used in Drug Development:
ZM 447439 is used in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for ZM 447439 delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Used in Pharmaceutical Industry:
ZM 447439 is used as a selective and potent inhibitor of Aurora B kinase in the pharmaceutical industry for the development of targeted cancer therapies.
Used in Biotechnology Industry:
ZM 447439 is used as a research tool in the biotechnology industry to study the molecular mechanisms of cell division and the role of Aurora B kinase in various cellular processes.
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
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
Check Digit Verification of cas no
The CAS Registry Mumber 331771-20-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,3,1,7,7 and 1 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 331771-20:
(8*3)+(7*3)+(6*1)+(5*7)+(4*7)+(3*1)+(2*2)+(1*0)=121
121 % 10 = 1
So 331771-20-1 is a valid CAS Registry Number.
InChI:InChI=1/C29H31N5O4/c1-36-26-18-24-25(19-27(26)38-15-5-12-34-13-16-37-17-14-34)30-20-31-28(24)32-22-8-10-23(11-9-22)33-29(35)21-6-3-2-4-7-21/h2-4,6-11,18-20H,5,12-17H2,1H3,(H,33,35)(H,30,31,32)
