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.
|Source||Concordia University (2015). Figure 9. ZM447439 (Abmole Bioscience)|
|Method||Inhibit Aurora B kinase|
|Cell Lines||MDCK cell lines|
|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 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.|
|Incubation time||72 h|
|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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||DMSO 53 mg/mL|
 Georgieva I, et al. Neuroendocrinology. ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines.
|Related Aurora Kinase Products|
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SNS-314 is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively and less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2.
|Aurora Kinase Inhibitor III
Aurora Kinase Inhibitor III is a strong and selective Aurora A kinase inhibitor with an IC50 of 42 nM.
SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively.
GSK1070916 is a reversible and ATP-competitive inhibitor of Aurora B/C with IC50 of 3.5 nM/6.5 nM. It displays >100-fold selectivity against the closely related Aurora A-TPX2 complex.
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