331771-20-1
331771-20-1 structure
- Name: ZM-447439
- Chemical Name: N-(4-((6-Methoxy-7-(3-Morpholinopropoxy)quinazolin-4-yl)aMino)phenyl)benzaMide
- CAS Number: 331771-20-1
- Molecular Formula: C29H31N5O4
- Molecular Weight: 513.588
- Catalog: Biochemical Inhibitor Cell Cycle Aurora Kinase Inhibitor
- Create Date: 2018-12-23 06:26:35
- Modify Date: 2024-01-02 12:33:26
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ZM-447439 is an aurora kinase inhibitor with IC50s of 110 and 130 nM for aurora A and B, respectively.
| Name | N-(4-((6-Methoxy-7-(3-Morpholinopropoxy)quinazolin-4-yl)aMino)phenyl)benzaMide |
|---|---|
| Synonyms |
ZM 447439
N-[4-({6-Methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl}amino)phenyl]benzamide Benzamide, N-[4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl]amino]phenyl]- TCMDC-125873 ZM-447439 N-[4-({6-Methoxy-7-[3-(morpholin-4-yl)propoxy]quinazolin-4-yl}amino)phenyl]benzamide ZM447439 |
| Description | ZM-447439 is an aurora kinase inhibitor with IC50s of 110 and 130 nM for aurora A and B, respectively. |
|---|---|
| Related Catalog | |
| Target |
Aurora A:110 nM (IC50) Aurora B:130 nM (IC50) |
| In Vitro | Cells treated with ZM-447439 progress through interphase, enter mitosis normally, and assemble bipolar spindles. However, chromosome alignment, segregation, and cytokinesis all fail. ZM-447439 inhibits cell division and inhibit mitotic phosphorylation of histone H3. ZM-447439 prevents chromosome alignment and segregation. ZM-447439 compromises spindle checkpoint function. ZM-447439 inhibits kinetochore localization of BubR1, Mad2, and Cenp-E[1]. Inhibition of Aurora kinase by ZM-447439 reduces histone H3 phosphorylation at Ser10 in Hep2 carcinoma cells. Multipolar spindles are induced in these ZM-treated G2/M-arrested cells with accumulation of 4N/8N DNA, similar to cells with genetically suppressed Aurora-B. ZM-447439 treatment induces cell apoptosis. ZM-447439 inhibition of Aurora kinase is potently in association with decrease of Akt phosphorylation at Ser473 and its substrates GSK3α/β phosphorylation at Ser21 and Ser9[2]. |
| Kinase Assay | 1 ng purified recombinant enzyme is added to a reaction cocktail containing buffer, 10 μM peptide substrate, 10 μM for Aurora A or 5 μM ATP for Aurora B, and 0.2 μCi γ[33P]ATP, and is then incubated at room temperature for 60 min. 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 Betaplate counter. No enzyme and no compound control values are used to determine the concentration of ZM-447439, which gave 50% inhibition of enzyme activity[1]. |
| Cell Assay | To determine cloning efficiency, MCF7 cells are plated in phenol red free DME plus 5% stripped serum, and are then treated with or without the anti-estrogen ICI 182780 at 1 μM for 48 h. ZM-447439 is then added at the indicated concentrations for 72 h. The cells are harvested, washed, and ∼400 cells plated in each well of a 6-well plate in complete media without ZM-447439. After 10 d, the colonies are fixed, stained with crystal violet, and counted. The cloning efficiency represents the number of colonies on ZM-447439-treated plates compared with DMSO-treated controls[1]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 639.7±55.0 °C at 760 mmHg |
| Melting Point | 117-120ºC |
| Molecular Formula | C29H31N5O4 |
| Molecular Weight | 513.588 |
| Flash Point | 340.7±31.5 °C |
| Exact Mass | 513.237610 |
| PSA | 97.84000 |
| LogP | 2.66 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.664 |
| Storage condition | Desiccate at RT |