ZM 447439 化学構造
分子量: 513.59

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Quality Control & MSDS

製品説明

  • Compare Aurora Kinase Inhibitors
    Aurora Kinase製品生物活性の比較
  • 研究分野
  • ZM 447439のメカニズム

製品の説明

生物活性

製品説明 ZM 447439は、オーロラ選択ATPです-競争的な阻害剤で、オーロラAキナーゼとオーロラBキナーゼに作用すると、IC50が それぞれ 110 nM と 130 nM,になる。
ターゲット Aurora A Aurora B
IC50 110 nM 130 nM [1]
In vitro試験 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試験
臨床試験
特集 An Aurora selective ATP-competitive inhibitor.

プロトコル (参考用のみ)

キナーゼアッセイ: [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.

細胞アッセイ: [2]

細胞株 BON, QGP-1 and MIP-101 cells
濃度 0-5 μM
反応時間 72 hours
実験の流れ 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download ZM 447439 SDF
分子量 513.59
化学式

C29H31N5O4

CAS No. 331771-20-1
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 103 mg/mL (200.54 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 N-(4-(6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-ylamino)phenyl)benzamide

カスタマーフィードバック (3)


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Rating
Source Mol Biol Cell, 2011, 22, 4227-35. ZM 447439 purchased from Selleck
Method Flow cytometry
Cell Lines HeLa Tet-on cells
Concentrations
Incubation Time 0-1 h
Results p31comet depletion did not block mitotic exit induced by Aurora B inhibitor ZM447439.

Click to enlarge
Rating
Source Dr. Yuanhong Chen of University of Nebraska. ZM 447439 purchased from Selleck
Method Western blot
Cell Lines HeLa cells
Concentrations 1 μM
Incubation Time 2 h
Results The results showed that ZM447439 inhibits both Aurora-B and –C kinases, but not Aurora-A kinase.

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. ZM 447439 purchased from Selleck
Method Western blot
Cell Lines
Concentrations 0-10 μM
Incubation Time
Results ZM447439 treatment resulted in a reduction of Histone H3 and Aurora A/B/C phosphorylation.

文献中の引用 (11)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
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