| CAS NO: | 331771-20-1 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 513.59 |
|---|---|
| Formula | C29H31N5O4 |
| CAS No. | 331771-20-1 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 103 mg/mL (200.5 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL |
| Synonyms | Synonym: ZM-447439; ZM 447439; ZM447439. Chemical Name: N-(4-((6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-yl)amino)phenyl)benzamide InChi Key: OGNYUTNQZVRGMN-UHFFFAOYSA-N InChi Code: 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) SMILES Code: O=C(NC1=CC=C(NC2=C3C=C(OC)C(OCCCN4CCOCC4)=CC3=NC=N2)C=C1)C5=CC=CC=C5 |
| In Vitro | In vitro activity: 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. Kinase Assay: 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 Assay: In BON, QGP-1 and MIP-101 cells, ZM 447439 time- and dose-dependently inhibited cell growth with IC50 values of 3 μM, 0.9 μM and 3 μM, respectively. |
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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Neuroendocrinology. 2010;91(2):121-30; J Cell Biol. 2003 Apr 28;161(2):267-80 |
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