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ZM-447439

产品号 S1103 公司名称 Selleck Chemicals
CAS号 331771-20-1 公司网站 http://www.selleckchem.com
分子式 C29H31N5O4 电 话 (877) 796-6397
分子量 513.58754 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 72511

产品价格信息

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产品别名

标题
ZM-447439
IUPAC标准名
N-[4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinazolin-4-yl}amino)phenyl]benzamide
IUPAC传统名
N-[4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinazolin-4-yl}amino)phenyl]benzamide

产品登记号

CAS号 331771-20-1

产品性质

作用靶点 Aurora Kinase
成盐信息 Free Base
溶解度 DMSO
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Canccer
Biological Activity
Description ZM-447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively.
Targets Aurora A Aurora B
IC50 110 nM 130 nM [1]
In Vitro 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. [1] 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. [2] 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. [3] A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity to cisplatin. [4]
In Vivo
Clinical Trials
Features ZM-447439 is an Aurora selective ATP-competitive inhibitor.
Protocol
Kinase Assay [1]
In vitro kinase assays 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 [2]
Cell Lines BON, QGP-1 and MIP-101 cells
Concentrations 0-5 μM
Incubation Time 72 hours
Methods Cell number is evaluated by crystal violet staining. In brief, cells in 96-well plates are fixed with 1% glutaraldehyde. Then cells are stained with 0.1% crystal violet. The unbound dye is removed by washing with water. Bound crystal violet is solubilized with 0.2% Triton X-100. Light extinction which increases linearly with the cell number is analyzed at 570 nm using an ELISA reader.
References
[1] Ditchfield C, et al. J Cell Biol. 2003, 161(2), 267-280.
[2] Georgieva I, et al. Neuroendocrinology. 2010, 91(2), 121-130.
[3] Teperek-Tkacz M, et al. Cell Cycle. 2010, 9(23), 4674-4687.
[4] Zhang L, et al. J Obstet Gynaecol Res. 2011, 37(6), 591-600.