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当前位置: 首页 > 产品中心 > Small_molecule > Medchemexpress/PD98059/HY-12028/50mg
商品详细Medchemexpress/PD98059/HY-12028/50mg
Medchemexpress/PD98059/HY-12028/50mg
Medchemexpress/PD98059/HY-12028/50mg
商品编号: HY-12028-10mM*1mLinDMSO
品牌: MedChemExp
市场价: ¥1320.00
美元价: 792.00
产地: 美国(厂家直采)
公司:
产品分类: 小分子
公司分类: Small_molecule
联系Q Q: 3392242852
电话号码: 4000-520-616
电子邮箱: info@ebiomall.com
商品介绍
PD98059isaMEKinhibitorwithIC50of5μM,alsosuppressesTCDDbindingtothearylhydrocarbonreceptor(AHR)withIC50of4μM.

CustomerValidation

  • Biomaterials.2017Mar22;130:14-27.
  • BrJCancer.2017Sep26;117(7):974-983.
  • CellMolLifeSci.2017Oct25.
  • HumMolGenet.2017Sep15;26(18):3553-3563.
  • JImmunol.2015Nov15;195(10):4873-83.
  • CellSignal.2017May26;37:31-39.
  • MolImmunol.2017May4;87:161-170.
  • PLoSOne.2017Sep25;12(9):e0185354.
  • MolCellBiochem.2017Aug12.
  • BiochemBiophysResCommun.2017Nov14.pii:S0006-291X(17)32258-1.
  • ExpTherMed.2017Apr;13(4):1353-1359.
  • BiomedicalResearch2017;28(8):3383-3386
  • ManchesterMetropolitanUniversity.09May2017.
Description

PD98059isaMEKinhibitorwithIC50of5μM,alsosuppressesTCDDbindingtothearylhydrocarbonreceptor(AHR)withIC50of4μM.

IC50&Target

IC50:5μM(MEK)[1]

InVitro

ConcentrationsofPD98059of≤20μMarenotcytotoxictoculturedMCF10A,MCF10A-Neo,andMCF10A-NeoTcells.However,PD98059isweaklycytostatictoallthreelinesatconcentrationsof≥10μM.TreatmentofMCF10A-NeoandMCF10A-NeoTcultureswithconcentrationsofPD98059upto20μMfor2-22hrdoesnotalterthetotalERKcontent.However,treatmentwithPD98059doesresultinconcentration-dependentreductionsintheduallyphosphorylatedformsofERK1andERK2.Within2hrofa10-μMtreatment,phosphorylatedERKcontentsarereduced~74%and~86%inMCF10A-NeoandMCF10A-NeoTcultures,respectively(IC50=1μM).Within22hroftreatment,phosphorylatedERKformsarealmostcompletelyeliminatedinbothcelllines[1].PD98059(PD098059)preventstheactivationofMAPKK1byRaforMEKkinaseinvitroatconcentrations(IC50=2-7μM).PD98059inhibitsboththeactivationandphosphorylationofMAPKK1invitrobyeitherc-RaforMEKkinasewithIC50valuesof4±2μM.IncubationofSwiss3T3cellswithPD98059(50μM)suppressedby80-90%theactivationofMAPKKinducedbyeachagoNIST,buttheactivationofc-Rafisenhanced2-3-fold[2].

InVivo

ThetreatmentofmicewithPD98059significantlyreducesthelevelofp-ERK1/2.Moreover,asignificantincreaseinthephospho-p38expressionisobservedinZymosan-treatedmiceat18hafterZymosanadministrationcomparedtothesham-operatedmice.ThetreatmentwithPD98059significantlyreducesthep38expression[3].RepeatedtreatmentwithPD98059attenuatesmechanicalallodyniameasuredbythevonFreytestthree(18.0g±0.8,n=10)andseven(20.21g±0.67,n=26)daysafterCCIincomparisontothevehicle-treatedCCI-exposedrats(15.1g±1.3,n=7and14.21g±0.44,n=28,respectively).RepeatedinjectionofPD98059diminishesthermalhyperalgesia,asisevaluatedbythecoldplatetest,three(17.5s±2.1,n=10)andseven(25.54s±1.03,n=26)daysfollowingCCIcomparedtovehicle-treatedCCI-exposedrats(11.5s±1.8,n=7and11.4s±0.88,n=28,respectively)[4].

References
  • [1].ReinersJJJr,etal.PD98059isanequipotentantagonistofthearylhydrocarbonreceptorandinhibitorofmitogen-activatedproteinkinasekinase.MolPharmacol.1998Mar;53(3):438-45.

    [2].AlessiDR,etal.PD098059isaspecificinhibitoroftheactivationofmitogen-activatedproteinkinasekinaseinvitroandinvivo.JBiolChem,1995,270(46),27489-27494.

    [3].DiPaolaR,etal.PD98059,aspecificMAPkinaseinhibitor,attenuatesmultipleorgandysfunctionsyndrome/failure(MODS)inducedbyzymosaninmice.PharmacolRes.2010Feb;61(2):175-87.

    [4].RojewskaE,etal.PD98059InfluencesImmuneFactorsandEnhancesOpioidAnalgesiainModelofNeuropathy.PLoSOne.2015Oct1;10(10):e0138583.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM3.7414mL18.7070mL37.4139mL
5mM0.7483mL3.7414mL7.4828mL
10mM0.3741mL1.8707mL3.7414mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

Kinasereactionsareperformedin50μLreactionvolumesandcontain50mMTris,pH7.4,10mMMgCl2,2mMEGTA,10μMATP(containing1μCiof3000Ci/mmol[γ-32P]ATP),7.6μgofGST-MEK1,7.2μgofGST-ERK1,and20μgofMBP.PD98059andotherflavonoidsareaddedtothereactionsmixturesimmediatelyaftertheadditionofGST-MEK1butbeforetheadditionofGST-ERK1andATP.ControlreactionscontainERK1andMBPbutnoMEK.Reactionmixturesareincubatedat30°Cfor15minbeforebeingstoppedbytheadditionofLaemmli’sSDSsamplebuffer.ProteinsareseparatedonSDS-15%polyacrylamidegels.Aftervacuumdryingofthegel,rADIoactivityisdetectedbyautoradiographyonX-rayfilmorphosphoimagingusingaBioRadGS-525MolecularImager[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[1]

PD98059isdissolvedinDMSOandstored,andthendilutedwithappropriatemedia(DMSO<0.1%) before="">[1].

TheMCF10A,MCF10A-Neo,andMCF10A-NeoTcelllinesareused.SubconfluentculturesaretreatedwithPD98059(0-100μM).ViABIlityofcellsaftertreatmentisassessedbyabilitytoexcludetrypanblue.CulturesearmarkedforRNAisolationarewashedtwicewithphosphate-bufferedsaline(2.7mMKCl,1.5mMKH2PO4,137mMNaCl,8mMNa2HPO4,pH7.2)atharvestingandstoredat-80°C[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[3][4]

PD98059ispreparedinnon-pyrogenicsaline(0.9%NaCl)(Mice)[3].
PD98059isdissolvedin75%DMSO(Rat)[4].

Mice[3]
MaleCDmice(20-22g)arerandomlyallocatedintothefollowinggroups:1.Zymosan+DMSOgroup.Micearetreatedintraperitoneally(i.p.)withZymosan(500mg/kg,sUSPendedinsalinesolution)andwiththevehicleforPD98059(10%DMSO,v/v)i.p.1and6hafterZymosanadministration(N=10).2.PD98059group.IdenticaltotheZymosan+DMSOgroupbutareadministeredPD98059(10mg/kg,i.p.bolus)at1and6hafterZymosan(N=10)insteadofDMSO.3.Sham+DMSOgroup.IdenticaltotheZymosan+DMSOgroupbutareadministeredsalinesolutioninsteadofZymosan(N=10).4.Sham+PD98059group.IdenticaltoSham+DMSOgroup,exceptfortheadministrationofPD98059(10mg/kgi.p.bolus)1and6haftersalineadministration(N=10).
Rat[4]
Therats(maleWistar,300-350g)areused.ThePD98059(2.5μg/5μL,i.t.)issingleorrepeatedpreemptivelyadministered16hand1hbeforeCCIandthenoncedailyfor7days.TheVehicle-treatedCCI-exposedratsreceive75%DMSOaccordingtothesameschedule.Thereisnosignificantdifferenceinpainbehaviorbetweenno-treatedandV(DMSO)-treatedCCI-exposedrats.ThismethodofPD98059orvehicleadministrationisusedthroughoutthestudyandisreferredtointhetextas“repeatedadministration”.Atday7thafterCCI30minafterPD98059administrationtactileallodyniaismeasuredusingvonFreytestandthermalhyperalgesiaisconductedusingcoldplatetest.Additionally,atday7thafterCCIthevehicle-treatedandPD98059-treatedratsreceiveasinglei.t.vehicle,Morphine(2.5μg/5μL)orBuprenorphine(2.5μg/5μL)injection30minafterPD98059,andthen30minlaterthevonFreyand/orcoldplatetestsarerepeated.Sincethedoseofmorphine2.5μg/5μLinnaiveratsproducesmaximalanalgesiceffectintail-flicktest.LowerdoseofMorphineareusedforco-administrationexperiments,sothatobservingthepossIBLeenhancementofopioideffectiveness.Thevehicle-treatedandPD98059-treatednaiverats(uninjuredrats)receiveasinglei.t.vehicle,Morphine(0.5μg/5μL)orBuprenorphine(2.5μg/5μL)injection30minafterPD98059,andthen30minlaterthetailflicktestisperformed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].ReinersJJJr,etal.PD98059isanequipotentantagonistofthearylhydrocarbonreceptorandinhibitorofmitogen-activatedproteinkinasekinase.MolPharmacol.1998Mar;53(3):438-45.

    [2].AlessiDR,etal.PD098059isaspecificinhibitoroftheactivationofmitogen-activatedproteinkinasekinaseinvitroandinvivo.JBiolChem,1995,270(46),27489-27494.

    [3].DiPaolaR,etal.PD98059,aspecificMAPkinaseinhibitor,attenuatesmultipleorgandysfunctionsyndrome/failure(MODS)inducedbyzymosaninmice.PharmacolRes.2010Feb;61(2):175-87.

    [4].RojewskaE,etal.PD98059InfluencesImmuneFactorsandEnhancesOpioidAnalgesiainModelofNeuropathy.PLoSOne.2015Oct1;10(10):e0138583.

MolecularWeight

267.28

Formula

C₁₆H₁₃NO₃

CASNo.

167869-21-8

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:16mg/mL;H2O:<0.01="">

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:99.45%