IC-87114-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIC-87114Cat.No.:HY-10110CASNo.:371242-69-2分⼦式:C₂₂H₁₉N₇O分⼦量:397.43作⽤靶点:PI3K作⽤通路:PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:10mg/mL(25.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5162mL12.5808mL25.1617mL5mM0.5032mL2.5162mL5.0323mL10mM0.2516mL1.2581mL2.5162mL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:≥1mg/mL(2.52mM);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%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.52mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.52mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性IC-87114⼀种有效的选择性PI3Kδ抑制剂，IC50为0.5μM。IC50&TargetPI3KδPI3KβPI3Kγ0.5μM(IC50)75μM(IC50)29μM(IC50)体外研究IC-87114(IC87114),ananalogoftheoriginalinhibitor,issynthesizedandtestedforPI3KδselectivityrelativetotheotherclassIPI3Ks.TheIC50ofIC87114forPI3Kδinhibitionis0.5μMwhereastheIC50valuesforPI3Kα,PI3Kβ,andPI3Kγare>100,75,and29μM,respectively.ThusIC87114is58-foldmoreselectiveforPI3KδrelativetoPI3Kγ,andover100-foldselectiverelativetoPI3KαandPI3Kβ.IC87114selectivelyantagonizesPI3Kδoveratleastaconcentrationrangeof0.3-10μM[1].IC-87114(10μM)isalsousedtoselectivelyinhibitPI3Kδcatalyticactivitytoaddressthisquestion.IC87114(10μM)effectivelyinactivatesAktinmacrophagesaftertreatmentfor1hour(n=6;P[2].体内研究TreatmentwithPD89059(10ꢀmg/kg),IC-87114(0.3ꢀmg/kg)andBAY11-7085(10ꢀmg/kg),significantly(P0.05).Ofnote,theobservedreductioninthehistopathologicalairwayremodelinginducedbyPD89059,IC-87114andBAY11-7085arelesseffectiveascomparedtothereductionseenwithAG1478andSU6656[3].PROTOCOLCellAssay[2]ThemurinemacrophagecelllineRAW264.7andperitonealmacrophagesfrombothtypesofmicearemaintainedinDulbecco'smodifiedEagle'smedium(DMEM)with10%fetalcalfserum(FCS).Culturesaremaintainedat37°Cinahumidifiedincubatorina95%O2plus5%CO2atmosphere.CellsaretreatedwithvariedconcentrationsofTNF-αandusedIC-87114(IC87114)toinhibitPtdIns(3,4,5)P3-dependentphosphorylationofAktbeforeTNF-αstimulationatearlytimepoints(30min)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]BALB/cmiceareimmunizedoncebyi.p.injectionof10ꢀµgovalbumin(OVA)in0.2ꢀmlofalu-Gel-Sonday0.Tendayslater,miceareintranasally(i.n.)challengedwithOVA(30ꢀµgin50ꢀµLPBS)orPBS,oncedaily,overfourconsecutivedays.ToinvestigateifERK1/2,PI3KδandNF-κBaresignalingeffectorsdownstreamofEGFRtransactivation,sixtreatmentgroups(A-F,10-30animalspergroup)areestablished.MiceingroupsAandBarepretreatedintranasallywith0.2mLofthevehicleforthedrugs.GroupsC,DandEarepretreatedwiththesamevolumeofthreedifferentdrugs(PD98059,IC-87114andBAY11-7085,respectively)at10ꢀmg/kg,10ꢀmg/kgand0.3ꢀmg/kgrespectively,andgroupFwithDexamethasone(1ꢀmg/kg),1ꢀhbeforeeach2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEi.n.challengewithOVA.Thesedosesarechosenfrompreviousstudieswheretheyareshowntobeeffective.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciSignal.2021Dec21;14(714):eabj0057.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SadhuC,etal.Essentialroleofphosphoinositide3-kinasedeltainneutrophildirectionalmovement.JImmunol.2003Mar1;170(5):2647-54.[2].ZhengL,etal.InactivationofPI3KδinducesvascularinjuryandpromotesaneurysmdevelopmentbyupregulatingtheAP-1/MMP-12pathwayinmacrophages.ArteriosclerThrombVascBiol.2015Feb;35(2):368-77.[3].El-HashimAZ,etal.Src-dependentEGFRtransactivationregulateslunginflammationviadownstreamsignalinginvolvingERK1/2,PI3Kδ/AktandNFκBinductioninamurineasthmamodel.SciRep.20