EED226-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEED226Cat.No.:HY-101117CASNo.:2083627-02-3分⼦式:C₁₇H₁₅N₅O₃S分⼦量:369.4作⽤靶点:HistoneMethyltransferase作⽤通路:Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥125mg/mL(338.39mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7071mL13.5355mL27.0709mL5mM0.5414mL2.7071mL5.4142mL10mM0.2707mL1.3535mL2.7071mL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。-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：0.5%HPMC>>1%Tween801/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:10mg/mL(27.07mM);Suspenedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.77mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.77mM);Suspendedsolution4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.77mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性EED226⼀种多梳抑制复合物2(PRC2)抑制剂，与胚胎外胚层发育(EED)上的K27me3⼝袋结合，在移植瘤⼩⿏模型中具有强的抗肿瘤活性[1]。EED226⼀种有效的，⼝服可⽣物利⽤的，选择性EED抑制剂[2]。当H3K27me0肽⽤作体外酶法测定的底物时，EED226抑制PRC2的IC50为23.4nM[3]。IC50&TargetIC50:23.4nM(PRC2)[3]体外研究EED226isahighlypotent,efficientandselectiveinhibitorofEZH2andEZH1evaluatedagainstabroadrangeofepigeneticandnon-epigenetictargets.ItpotentlyreducesglobalH3K27Me3markincellsanddemonstratesselectivelycellkillingeffectsincellscarryingaheterozygousY641Nmutation.EED226hasmoderatepermeabilityasthemeasuredinCaco-2cellsatA→B=3.0x10-6cm/s,withaneffluxratioat7.6[2].Intheinvitroenzymaticassays,EED226inhibitedPRC2withanIC50of53.5nMwhenthemononucleosomeisusedasthesubstrate,withthestimulatoryH3K27me3addedat1×Kact(1.0μM)[3].体内研究EED226inducesrobustandsustainedtumorregressioninEZH2MUTpre-clinicalDLBCLmodel.InCD-1mice,dosingofEED226for14daysat300mg/kgbidiswelltoleratedwithnoapparentadverseeffects.Ithasverylowinvivoclearance,andapproximately100%oralbioavailability.EED226haslowvolumeofdistribution(0.8L/kg),reasonableterminalt1/2(2.2h),andmoderateplasmaproteinbinding(PPB)[2].PROTOCOLAnimalMice:EED226isformulatedasasuspensionin0.5%PHMC+0.5%Tween80inwaterandadministeredAdministration[2]orallybygavageatadosevolumeof10mL/kgtothetumorbearingmice.Attheendpoint,theanimalsisgiventhefirstdoseadministration.ForPKanalysis100μLofbloodsamplesarecollectedfromeachanimalbyorbitalsinusbleeding.ForanalysisofcompoundlevelsandPDintissues,tumorsarecollected4hrposttreatmentandfrozenimmediatelyinliquidnitrogen.Tumorandbodyweightchangedataareanalyzedstatistically[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•GenomeBiol.2020Aug6;21(1):195.•CellDeathDis.2022Feb15;13(2):155.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•FrontOncol.2019Jan14;8:679.•ACSInfectDis.2020Jul10;6(7):1719-1733.•SciRep.2020Sep16;10(1):15201.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HuangY,etal.DiscoveryofFirst-in-Class,Potent,andOrallyBioavailableEmbryonicEctodermDevelopment(EED)InhibitorwithRobustAnticancerEfficacy.JMedChem.2017Mar23;60(6):2215-2226.[2].LiL,etal.DiscoveryandMolecularBasisofaDiverseSetofPolycombRepressiveComplex2InhibitorsRecognitionbyEED.PLoSOne.2017Jan10;12(1):e0169855.[3].QiW,etal.AnallostericPRC2inhibitortargetingtheH3K27me3bindingpocketofEED.NatChemBiol.2017Apr;13(4):381-388.McePdfHe