Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIC-87114Cat.No.:HY-10110CASNo.:371242-69-2分?式:C??H??N?O分?量:397.43作?靶點(diǎn):PI3K作?通路:PI3K/Akt/mTOR儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:10mg/mL(25.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5162mL12.5808mL25.1617mL5mM0.5032mL2.5162mL5.0323mL10mM0.2516mL1.2581mL2.5162mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1mg/mL(2.52mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.52mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.52mM);ClearsolutionBIOLOGICALACTIVITY?物活性IC-87114?種有效的選擇性PI3Kδ抑制劑，IC50為0.5μM。IC50&TargetPI3KδPI3KβPI3Kγ0.5μM(IC50)75μM(IC50)29μM(IC50)體外研究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].體內(nèi)研究TreatmentwithPD89059(10?mg/kg),IC-87114(0.3?mg/kg)andBAY11-7085(10?mg/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.injectionof10?μgovalbumin(OVA)in0.2?mlofalu-Gel-Sonday0.Tendayslater,miceareintranasally(i.n.)challengedwithOVA(30?μgin50?μLPBS)orPBS,oncedaily,overfourconsecutivedays.ToinvestigateifERK1/2,PI3KδandNF-κBaresignalingeffectorsdownstreamofEGFRtransactivation,sixtreatmentgroups(A-F,10-30animalspergroup)areestablished.MiceingroupsAandBarepretreatedintranasallywith0.2mLofthevehicleforthedrugs.GroupsC,DandEarepretreatedwiththesamevolumeofthreedifferentdrugs(PD98059,IC-87114andBAY11-7085,respectively)at10?mg/kg,10?mg/kgand0.3?mg/kgrespectively,andgroupFwithDexamethasone(1?mg/kg),1?hbeforeeach2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEi.n.challengewithOVA.Thesedosesarechosenfrompreviousstudieswheretheyareshowntobeeffective.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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