331771-20-1 Usage
Description
Different sources of media describe the Description of 331771-20-1 differently. You can refer to the following data:
1. 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.
2. 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.
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
Chemical Properties
Pale Yellow Solid
Uses
Different sources of media describe the Uses of 331771-20-1 differently. You can refer to the following data:
1. 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.
2. 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.
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)
