BAY-299-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBAY-299Cat.No.:HY-107424CASNo.:2080306-23-4分⼦式:C₂₅H₂₃N₃O₄分⼦量:429.47作⽤靶点:EpigeneticReaderDomain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:25mg/mL(58.21mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3285mL11.6423mL23.2845mL5mM0.4657mL2.3285mL4.6569mL10mM0.2328mL1.1642mL2.3285mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.82mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.82mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BAY-299⼀种⾮常有效的双重抑制剂，抑制BRPF2溴结构域(BD)，TAF1BD2，和TAF1LBD2，IC50分别为67nM，8nM和106nM。IC50&TargetBRPF2BDBRPF1BDBRPF3BDTAF1BD267nM(IC50)3150nM(IC50)5550nM(IC50)8nM(IC50)TAF1LBD2106nM(IC50)体外研究BAY-299isadualinhibitorofthebromodomainandPHDfinger(BRPF)familymemberBRPF2andtheTATAboxbindingprotein-associatedfactorsTAF1andTAF1L.TR-FRETassaysshowedthatBAY-299isapotentinhibitorofBRPF2BDwithanIC50of67nM,andaselectivityof47-and83-foldoverBRPF1andBRPF3BDs.TheprofileofBAY-299isfurtherconfirmedbyAlphaScreenassay,whereanIC50of97nMandaselectivityof23-and25-foldoverBRPF1andBRPF3BDsaremeasured.NanoBRETexperimentsshowthattheinteractionofBRPF2BDwithhistonesH4andH3.3isblockedbyBAY-299withIC50valuesof575and825nM,respectively.ForTAF1BD2,theIC50valuesare970and1400nM,respectively.NoinhibitoryeffectisobservedfortheinteractionbetweenBRPF1orBRD4andhistoneH4upto10μMforBAY-299.BAY-299inhibitsMOLM-13,MV4-11,769-P,Jurkat,NCI-H526,CHL-1,and5637cellsproliferationwithGI50sof1060,2630,3210,3900,6860,7400,and7980nM,respectively[1].体内研究StudiesoftheinvivopharmacokineticpropertiesofBAY-299inratrevealthatbloodclearanceislow(ca.17%ofhepaticbloodflow),volumeofdistributioninsteady-statehigh,terminalhalf-lifelongtoverylong(t1/2=10h),andbioavailabilityhigh(F=73%).Invivobloodclearanceisasanticipatedbasedonratlivermicrosomevaluesbutlowerthanexpectedbasedonhepatocytedata[1].PROTOCOLCellAssay[1]MOLM-13,MV4-11,769-P,Jurkat,NCI-H526,CHL-1,and5637celllinesaretreatedwithBAY-299whileinthelogarithmicgrowthphase,andtheirviabilityisdeterminedbyAlamarBluestaining[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats[1]Administration[1]BAY-299isadministeredtothreemaleWistarratsperarm,eitherintravenouslyorintragastrallyformulatedassolutions.BAY-299isgivenasi.v.bolus,andbloodsamplesaretakenat2min,8min,15min,30min,45min,1h,2h,4h,6h,8h,and24hafterdosing.Forpharmacokineticsafterintragastraladministration,BAY-299isgivenintragastrallytofastedratsandbloodsamplesaretakenat5min,15min,30min,45min,1h,2h,4h,6h,8h,and24hafterdosing.Bloodiscollectedintolithium-heparintubesandcentrifugedfor15min2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEat3000rpm[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•TranslCancerRes.2021Dec;10(12):5307-5318.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BouchéL,etal.BenzoisoquinolinedionesasPotentandSelectiveInhibitorsofBRPF2andTAF1/TAF1LBromodomains.JMedChem.2017May11;60(9):4002-4022.McePdfHe