ZM447439 is an Aurora kinase B inhibitor, suppresses the growth of cervical cancer SiHa cells and enhances the chemosensitivity to cisplatin. Aurora family kinases play roles in several mitotic processes, including the G2/M transition, mitotic spindle organization, chromosome segregation, and cytokinesis. ZM447439 has dramatic effects on chromosome morphology and spindle dynamics. ZM-447439 can reduce the number of SiHa cells, increase the volume of cells and lead to apoptosis. The growth of SiHa cells treated with ZM447439 was inhibited in dose- and time-dependent manners. ZM447439 significantly inhibited the expression of Aurora-B and H3-P protein (P < 0.05). ZM-447439 selectively over a range of other kinases such as Cdk1 and PLK1 (up to 10mM). Additionally, aurora kinase inhibition by ZM447439 potently induced apoptosis, which was accompanied by DNA fragmentation and caspase 3 and 7 activation.
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Source | Concordia University (2015). Figure 9. ZM447439 (Abmole Bioscience) |
| Method | Inhibit Aurora B kinase | |
| Cell Lines | MDCK cell lines | |
| Concentrations | 1 μM | |
| Incubation Time | 20-‐40 min | |
| Results | Upon treating MDCK cells with an 35 Aurora B inhibitor, ZM447439, we found that the number asymmetrically ingressing cells was not statistically changed in comparison to control cells |
| Cell Experiment | |
|---|---|
| Cell lines | MCF7 cells |
| Preparation method | Cell cycle analysis and cloning assays. DNA content and mitotic index measurements and synchronization of TA-HeLa cells at G1/S using a double thymidine block were done as described previously (Taylor and McKeon, 1997). To determine cloning efficiency, MCF7 cells were plated in phenol red free DME plus 5% stripped serum (HyClone), and were then treated with or without the anti-estrogen ICI 182780 at 1 μM for 48 h. ZM447439 was then added at the indicated concentrations for 72 h. The cells were harvested, washed, and ∼400 cells plated in each well of a 6-well plate in complete media without ZM447439. After 10 d, the colonies were fixed, stained with crystal violet, and counted. The cloning efficiency represents the number of colonies on ZM447439-treated plates compared with DMSO-treated controls. |
| Concentrations | 0~5 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | MOLM13 cells in murine xenograft model |
| Formulation | 3 M Tris, pH 9.0, at a concentration of 2.5 mg/mL |
| Dosages | 5 mg/kg 4 times a week for 2 weeks |
| Administration | intraperitoneal injection |
| Molecular Weight | 513.59 |
| Formula | C29H31N5O4 |
| CAS Number | 331771-20-1 |
| Solubility (25°C) | DMSO 53 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Aurora Kinase Products |
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Aurora Kinases-IN-4 is a covalent and ATP competitive aurora kinase A inhibitor (IC50: 1.7 nM). |
| Derrone
Derrone, a prenylated isoflavones, is an Aurora kinase inhibitor, with IC50 values of 6 and 22.3 μM against Aurora B and Aurora A, respectively. Derrone shows anti-tumor activity. |
| CD532 hydrochloride
CD532 hydrochloride is a potent Aurora A kinase inhibitor with an IC50 of 45 nM. CD532 hydrochloride has the dual effect of blocking Aurora A kinase activity and driving degradation of MYCN. CD532 hydrochloride also can directly interact with AURKA and induces a global conformational shift. CD532 hydrochloride can be used for the research of cancer. |
| Aurora kinase inhibitor-2
Aurora kinase inhibitor-2 is a selective and ATP-competitive Aurora kinase inhibitor with IC50s of 310 nM and 240 nM for Aurora A and Aurora B, respectively. |
| AAPK-25
AAPK-25 is a potent and selective Aurora/PLK dual inhibitor with anti-tumor activity, which can cause mitotic delay and arrest cells in a prometaphase, reflecting by the biomarker histone H3Ser10 phosphorylation and followed by a surge in apoptosis. AAPK-25 targets Aurora-A, -B, and -C with Kd values ranging from 23-289 nM, as well as PLK-1, -2, and -3 with Kd values ranging from 55-456 nM. |
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