Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGNA002Cat.No.:HY-101508CASNo.:1385035-79-9分?式:C??H??NO?分?量:701.89作?靶點:HistoneMethyltransferase作?通路:Epigenetics儲存?式:-20°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(35.62mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.4247mL7.1236mL14.2472mL5mM0.2849mL1.4247mL2.8494mL10mM0.1425mL0.7124mL1.4247mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(1.78mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.25mg/mL(1.78mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性GNA002?種有效，選擇性的，共價EZH2抑制劑，對EZH2的IC50為1.1μM。GNA002可以特異性，共價結(jié)合EZH2-SET結(jié)構(gòu)域內(nèi)的Cys668，通過Hsp70相互作?蛋?(CHIP)介導(dǎo)的泛素化的COOH末端引發(fā)EZH2降解。GNA002有效降低EZH2介導(dǎo)的H3K27三甲化，重新激活polycomb阻遏復(fù)合物2(PRC2)沉默的腫瘤抑制因。IC50&TargetEZH21.1μM(IC50)體外研究GNA002(10μM;72hours)clearlyinhibitstheproliferationofnumerouscancercelllineswithIC50sof0.070μMand0.103μMforMV4-11andRS4-11[1].GNA002(2μM;24hours)demonstratesanelevatedcapacitytoinducecelldeathinhumancancercells[1].GNA002(0.1-4μM;48hours)efficientlyreducesEZH2-mediatedH3K27trimethylationinCal-27headandneckcancercells[1].CellProliferationAssay[1]CellLine:NumerouscancercelllinesConcentration:10μMIncubationTime:72hoursResult:InhibitedtheproliferationofnumerouscancercelllineswithIC50sof0.070μMand0.103μMforMV4-11andRS4-11.ApoptosisAnalysis[1]CellLine:HN-4andCal-27headandneckcancercellsConcentration:2μMIncubationTime:24hoursResult:Inducedcellularapoptosisinhumancancercells.WesternBlotAnalysis[1]CellLine:Cal-27headandneckcancercellsConcentration:0.1,0.2,0.5,1,2,4μMIncubationTime:48hoursResult:ReducedH3K27Me3levels.體內(nèi)研究GNA002(oraladministration;100mg/kg;daily)significantlydecreasesthevolumesofCal-27-derivedtumors2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEandreducesH3K27Me3levelsintumortissues.GNA002alsosignificantlysuppressestheinvivotumorgrowthderivedfromthexenograftedA549lungcancercells,DaudiandPfeiffercells.GNA002inhibitstheaberrantoncogenicfunctionsofEZH2,thusinhibitingtumorgrowthinvivo,atleastinthexenograftexperimentalmodel[1].AnimalModel:MaleBALB/CNudemiceaged30-35daysandweighing18-22g,bearingCal-27xenografttumors[1]Dosage:100mg/kgAdministration:Oraladministration;dailyResult:DecreasedthesizeandweightoftumorsformedbyCal-27cells.REFERENCES[1].WangX,etal.AcovalentlyboundinhibitortriggersEZH2degradationthroughCHIP-mediatedubiquitination.EMBOJ.2017May,36(9):1243-1260.McePdfHeightCaution:Producthasnotbeenfully