Hesperadin - Aurora Kinase 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEHesperadinCat. No.: HY-12054CAS No.: 422513-13-1分式: CHNOS分量: 516.65作靶點(diǎn): Aurora Kinase; Autophagy作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy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) DM

2、SO : 100 mg/mL (193.55 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.9355 mL 9.6777 mL 19.3555 mL5 mM 0.3871 mL 1.9355 mL 3.8711 mL10 mM 0.1936 mL 0.9678 mL 1.9355 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)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液

3、，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)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 (4.84 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.84 mM); Clear solution1/3 Master of Small Molecul

4、es 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Hesperadin是ATP競(jìng)爭(zhēng)型的極光激酶 (aurora B) 抑制劑，IC50值為250 nM。IC50 & Target Aurora B250 nM (IC50)體外研究 Hesperadin also inhibits other kinases such as AMPK, Lck, MKK1, MAPKAP-K1, CHK1, and PHK at 1 Mdrug concentration. Hesperadin causes polyploidy in HeLa cells. Hespe

5、radin-treated HeLa cells showalignment and segregation defects, but sister chromatid separation is intact. Hesperadin causes defects inmitosis and cytokinesis. Hesperadin inhibits Aurora B. Immunofluorescence microscopy reveals thatHesperadin-treated cells in which chromosomes are stretched toward o

6、pposite poles, i.e., which haveentered anaphase, fail to assemble a central spindle and to properly localize the human centralspindlinsubunits CYK-4 and MKLP1 1. Hesperadin inhibits multiple human clinical isolates of influenza A and Bviruses with single to submicromolar efficacy, including oseltami

7、vir-resistant strains. Mechanistic studiesreveal that hesperadin inhibits the early stage of viral replication by delaying the nuclear entry of viralribonucleoprotein complex, thereby inhibiting viral RNA transcription and translation as well as viral proteinsynthesis 2. Hesperadin inhibits cell cel

8、l proliferation due to appearance of multiple mitotic defects causedby Aurora B activity reduction and elimination of checkpoint proteins-such as hBUBR1 and CENP-E-fromkinetochores of mitotic chromosomes 3.PROTOCOLKinase Assay 1 The kinase assay is performed with 10 L beads in 20 L kinase buffer con

9、taining 5 g histone H1, 1 M ATP,1 Ci 32PATP, and the appropriate concentration of Hesperadin or DMSO for 30 min at 37C. SDS samplebuffer is added, and samples are boiled and resolved by SDS. The gel is dried, and the radioactivesignal is detected by PhosphorImager analysis 1.MCE has not independentl

10、y confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 To determine cellular cytotoxicity of Hesperadin, 200 L fresh DMEM (without FBS) medium containing serialhalf-log diluted Hesperadin is added to each well. After incubating for 48 h with 5% CO2 in the cell cultureinc

11、ubator at 37 C, the medium is removed and 100 L DMEM medium containing 40 g/mL neutral red isadded. The solution is incubated for another 4 h at 37 C in the cell culture incubator. The medium isremoved and the amount of neutral red that is taken by the viable cells is dissolved by adding 100 L ofdes

12、taining solution (50% ethanol, 49% H2O, and 1% acetic acid). The absorbance of the solution at 540 nmis determined 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Hauf S, et al. The small molecule Hesperadin reveals a role for Aurora B in

13、 correcting kinetochore-microtubule attachment and inmaintaining the spindle assembly checkpoint. J Cell Biol. 2003 Apr 28;161(2):281-94.2. Hu Y, et al. Chemical Genomics Approach Leads to the Identification of Hesperadin, an Aurora B Kinase Inhibitor, as a Broad-Spectrum2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEInfluenza Antiviral. Int J Mol Sci. 2017 Sep 8;18(9).3. Ladygina NG, et al. Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells. Biomed Khim. 2005Mar-Apr;51(2):17