EED226-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEED226Cat.No.:HY-101117CASNo.:2083627-02-3分?式:C??H??N?O?S分?量:369.4作?靶點(diǎn):HistoneMethyltransferase作?通路:Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥125mg/mL(338.39mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.7071mL13.5355mL27.0709mL5mM0.5414mL2.7071mL5.4142mL10mM0.2707mL1.3535mL2.7071mL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；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(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，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑：0.5%HPMC>>1%Tween801/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:10mg/mL(27.07mM);Suspenedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.77mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.77mM);Suspendedsolution4.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.77mM);ClearsolutionBIOLOGICALACTIVITY?物活性EED226?種多梳抑制復(fù)合物2(PRC2)抑制劑，與胚胎外胚層發(fā)育(EED)上的K27me3?袋結(jié)合，在移植瘤??模型中具有強(qiáng)的抗腫瘤活性[1]。EED226?種有效的，?服可?物利?的，選擇性EED抑制劑[2]。當(dāng)H3K27me0肽?作體外酶法測(cè)定的底物時(shí)，EED226抑制PRC2的IC50為23.4nM[3]。IC50&TargetIC50:23.4nM(PRC2)[3]體外研究EED226isahighlypotent,efficientandselectiveinhibitorofEZH2andEZH1evaluatedagainstabroadrangeofepigeneticandnon-epigenetictargets.ItpotentlyreducesglobalH3K27Me3markincellsanddemonstratesselectivelycellkillingeffectsincellscarryingaheterozygousY641Nmutation.EED226hasmoderatepermeabilityasthemeasuredinCaco-2cellsatA→B=3.0x10-6cm/s,withaneffluxratioat7.6[2].Intheinvitroenzymaticassays,EED226inhibitedPRC2withanIC50of53.5nMwhenthemononucleosomeisusedasthesubstrate,withthestimulatoryH3K27me3addedat1×Kact(1.0μM)[3].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?GenomeBiol.2020Aug6;21(1):195.?CellDeathDis.2022Feb15;13(2):155.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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