GNA002-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGNA002Cat.No.:HY-101508CASNo.:1385035-79-9分⼦式:C₄₂H₅₅NO₈分⼦量:701.89作⽤靶点:HistoneMethyltransferase作⽤通路:Epigenetics储存⽅式:-20°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性数据体外实验DMSO:25mg/mL(35.62mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.4247mL7.1236mL14.2472mL5mM0.2849mL1.4247mL2.8494mL10mM0.1425mL0.7124mL1.4247mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(1.78mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.25mg/mL(1.78mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性GNA002⼀种有效，选择性的，共价EZH2抑制剂，对EZH2的IC50为1.1μM。GNA002可以特异性，共价结合EZH2-SET结构域内的Cys668，通过Hsp70相互作⽤蛋⽩(CHIP)介导的泛素化的COOH末端引发EZH2降解。GNA002有效降低EZH2介导的H3K27三甲化，重新激活polycomb阻遏复合物2(PRC2)沉默的肿瘤抑制因。IC50&TargetEZH21.1μM(IC50)体外研究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.体内研究GNA002(oraladministration;100mg/kg;daily)significantlydecreasesthevolumesofCal-27-derivedtumors2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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