For research use only. Not for therapeutic Use.
ZM 447439 (Cat No.:I003196) is a potent and selective Aurora kinase inhibitor. Aurora kinases are a family of serine/threonine protein kinases involved in regulating cell division and mitosis. ZM 447439 specifically targets Aurora kinases A and B, inhibiting their activity and disrupting proper cell division. This compound has shown efficacy in preclinical studies against various cancer types by inducing cell cycle arrest, mitotic defects, and apoptosis in cancer cells. ZM 447439 has been investigated for its potential as an anti-cancer therapeutic and has demonstrated promising results in inhibiting tumor growth. Further research is being conducted to explore its therapeutic applications and potential combination strategies with other anti-cancer agents.
| Catalog Number | I003196 |
| CAS Number | 331771-20-1 |
| Synonyms | N-[4-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]phenyl]benzamide |
| Molecular Formula | C₂₉H₃₁N₅O₄ |
| Purity | ≥95% |
| Target | Epigenetics |
| Solubility | DMSO ≥100mg/mL Water <1.2mg/mL Ethanol ≥45mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 110 nM( for Aurora A); 130 nM (for Aurora B) |
| IUPAC Name | N-[4-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]phenyl]benzamide |
| InChI | InChI=1S/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) |
| InChIKey | OGNYUTNQZVRGMN-UHFFFAOYSA-N |
| SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)NC(=O)C4=CC=CC=C4)OCCCN5CCOCC5 |
| Reference | 1:Cell Cycle. 2008 May 15;7(10):1473-9. Epub 2008 Mar 12. ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensional culture.Long ZJ,Xu J,Yan M,Zhang JG,Guan Z,Xu DZ,Wang XR,Yao J,Zheng FM,Chu GL,Cao JX,Zeng YX,Liu Q, PMID: 18418083 DOI: 10.4161/cc.7.10.5949 </br><span>Abstract:</span> Mitotic Aurora kinases are essential for accurate chromosome segregation during cell division. Forced overexpression of Aurora kinase results in centrosome amplification and multipolar spindles, causing aneuploidy, a hallmark of cancer. ZM447439 (ZM), an Aurora selective ATP-competitive inhibitor, interferes with the spindle integrity checkpoint and chromosome segregation. Here, we showed that inhibition of Aurora kinase by ZM reduced histone H3 phosphorylation at Ser10 in Hep2 carcinoma cells. Multipolar spindles were induced in these ZM-treated G(2)/M-arrested cells with accumulation of 4N/8N DNA, similar to cells with genetically suppressed Aurora-B. Cells subsequently underwent apoptosis, as assessed by cleavage of critical apoptotic associated protein PARP. Hep2 cells formed a tumor-like cell mass in 3-dimensional matrix culture; inhibition of Aurora kinase by ZM either destructed the preformed cell mass or prevented its formation, by inducing apoptotic cell death as stained for cleaved caspase-3. Lastly, ZM inhibition of Aurora kinase was potently in association with decrease of Akt phosphorylation at Ser473 and its substrates GSK3alpha/beta phosphorylation at Ser21 and Ser9. Together, we demonstrated that Aurora kinase served as a potential molecular target of ZM for more selective therapeutic cancer treatment. |
