1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEZM-447439Cat. No.: HY-10128CAS No.: 331771-20-1分式: CHNO分量: 513.59作靶點(diǎn): Aurora Kinase作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (194.71 m

2、M)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.9471 mL 9.7354 mL 19.4708 mL5 mM 0.3894 mL 1.9471 mL 3.8942 mL10 mM 0.1947 mL 0.9735 mL 1.9471 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)

3、實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.87 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.87 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBI

4、OLOGICAL ACTIVITY物活性 ZM-447439是極光激酶 (aurora) 抑制劑，對(duì)aurora A和B的 IC50 值分別為110和130 nM。IC50 & Target Aurora A Aurora B110 nM (IC50) 130 nM (IC50)體外研究 Cells treated with ZM-447439 progress through interphase, enter mitosis normally, and assemble bipolarspindles. However, chromosome alignment, segregation,

5、 and cytokinesis all fail. ZM-447439 inhibits celldivision and inhibit mitotic phosphorylation of histone H3. ZM-447439 prevents chromosome alignment andsegregation. ZM-447439 compromises spindle checkpoint function. ZM-447439 inhibits kinetochorelocalization of BubR1, Mad2, and Cenp-E 1. Inhibition

6、 of Aurora kinase by ZM-447439 reduces histone H3phosphorylation at Ser10 in Hep2 carcinoma cells. Multipolar spindles are induced in these ZM-treatedG2/M-arrested cells with accumulation of 4N/8N DNA, similar to cells with genetically suppressed Aurora-B.ZM-447439 treatment induces cell apoptosis.

7、ZM-447439 inhibition of Aurora kinase is potently in associationwith decrease of Akt phosphorylation at Ser473 and its substrates GSK3/ phosphorylation at Ser21 andSer9 2.PROTOCOLKinase Assay 1 1 ng purified recombinant enzyme is added to a reaction cocktail containing buffer, 10 M peptide substrate

8、,10 M for Aurora A or 5 M ATP for Aurora B, and 0.2 Ci 33PATP, and is then incubated at roomtemperature for 60 min. Reactions are stopped by addition of 20% phosphoric acid, and the products arecaptured on P30 nitrocellulose filters and assayed for incorporation of 33P with a Betaplate counter. Noen

9、zyme and no compound control values are used to determine the concentration of ZM-447439, which gave50% inhibition of enzyme activity 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 To determine cloning efficiency, MCF7 cells are plated i

10、n phenol red free DME plus 5% stripped serum, andare then treated with or without the anti-estrogen ICI 182780 at 1 M for 48 h. ZM-447439 is then added atthe indicated concentrations for 72 h. The cells are harvested, washed, and -400 cells plated in each well of a6-well plate in complete media with

11、out ZM-447439. After 10 d, the colonies are fixed, stained with crystalviolet, and counted. The cloning efficiency represents the number of colonies on ZM-447439-treated platescompared with DMSO-treated controls 1.MCE has not independently confirmed the accuracy of these methods. They are for refere

12、nce only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Ditchfield C, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. JCell Biol. 2003 Apr 28;161(2):267-80.2. Long ZJ, et al. ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensionalculture. Cell Cycle. 2008May 15;7(10):1473-9.McePdfHeight