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Medchemexpress/MG-132/HY-13259/10mg

MG-132isapotent,non-specific20Sproteasomeinhibitor,withIC50of24.2nMfortheβ5chymotrypsin-likeactivesite.

CustomerValidation

  • CancerLett.2017Dec1;410:112-123.
  • Oncotarget.2016May10;7(19):27176-84.
  • SciRep.2017Jul5;7(1):4738.
  • SciRep.2017Jun7;7(1):2929.
  • JInorgBiochem.2017Jul19;175:92-100.
  • BiochemBiophysResCommun.2017Sep2;490(4):1168-1175.
  • CanJPhysiolPharmacol.2016Nov30:1-11.
  • CanJPhysiolPharmacol.2016Sep19.
  • ActaNeuropatholCommun.2017Sep6;5(1):67.
  • BloodAdvances.20171:1773-1785.
  • HarvardMedicalSchoolLINCSLIBRARY
Description

MG-132isapotent,non-specific20Sproteasomeinhibitor,withIC50of24.2nMfortheβ5chymotrypsin-likeactivesite.

IC50&Target

IC50:24.2nM(chymotrypsin-likeactivity)[1]

InVitro

Dose-dependentinhibitionofcellgrowthisobservedinHeLacellswithanIC50ofapproximately5μMMG132for24h.MG132inhibitsthegrowthofHeLacellsviainducingthecellcyclearrestaswellastriggeringapoptosis[2].MG-132inhibitsC6gliomacellproliferationinatime-anddose-dependentmanner(theIC50valueat24his18.5μM).MG-132(18.5μM)suppressestheproteasomeactivitybyabout70%at3h.MG-132inducesapoptosisviadown-regulationofantiapoptoticproteinsBcl-2andXIAP,up-regulationofpro-apoptoticproteinBaxandcaspase-3,andproductionofcleavedC-terminal85kDaPARP.MG-132alsocausesamorethan5-foldincreaseofreactiveoxygenspecies[3].TheIC50ofMG-132againstHeLa,CaSki,andC33AcervicalcancercellsviABIlityafter48hofincubationis2.1,3.2,and5.2μM,respectively[4].

InVivo

TheinvivoantitumoractivityofMG-132againstcervicalcancerisexaminedusings.c.xenograftmodels.MG-132isinjectedat1mg/kgusingthefollowingschedule:days1,4,8,12,1518,23,and26formicebearingHeLatumors.ThegrowthinhibitionratesofMG132comparedtocontrolis49%[4].MG-132(i.p.,0.1mg/kg/day)attenuatespressure-overload-inducedcardiachypertrophyandimprovescardiacfunctioninaBDominalaorticbanding(AAB)ratsthroughregulationofERK1/2andJNK1signalingpathways[5].

References
  • [1].BraunHA,etal.Tripeptidemimeticsinhibitthe20Sproteasomebycovalentbondingtotheactivethreonines.JBiolChem.2005Aug5;280(31):28394-401.

    [2].HanYH,etal.TheeffectofMG132,aproteasomeinhibitoronHeLacellsinrelationtocellgrowth,reactiveoxygenspeciesandGSH.OncolRep.2009Jul;22(1):215-21.

    [3].FanWH,etal.ProteasomeinhibitorMG-132inducesC6gliomacellapoptosisviaoxidativestress.ActaPharmacolSin.2011May;32(5):619-25.

    [4].MatsumotoY,etal.EnhancedefficacyagainstcervicalcarcinomasthroughpolymericmicellesphysicallyincorporatingtheproteasomeinhibitorMG132.CancerSci.2016Jun;107(6):773-81.

    [5].ChenB,etal.MG132,aproteasomeinhibitor,attenuatespressure-overload-inducedcardiachypertrophyinratsbymodulationofmitogen-activatedproteinkinasesignals.ActaBiochimBiophysSin(Shanghai).2010Apr;42(4):253-8.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.1025mL10.5126mL21.0252mL
5mM0.4205mL2.1025mL4.2050mL
10mM0.2103mL1.0513mL2.1025mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[3]

Aftergrowingonsix-wellplates(3×105cells/well)for24h,C6gliomacellsaretreatedwitheitherPBS(control)or18.5μMMG-132for3,6,12,or24hat37°C.CellsarethoroughlyscrapedfromtheculturedisheswithacellscraperandwashedwithcoldPBS.Aftercentrifugationfor10minat800×g,thecellpelletsaresUSPendedinice-coldbuffer(50mMTris-HCl,pH7.5,20μMATP,5mMMgCl2,1mMdithiothreitol,and20%glycerol)andhomogenizedwithaPyrexglassmicrohomogenizer(20strokes).Thehomogenateiscentrifugedat15000×gfor10minat4°Ctoobtainsupernatant.Proteinconcentrationisdeterminedusingproteinassaykits.Atotalof10μL(1μg/μL)ofeachfreshlymadesupernatantisincubatedina96-wellplateat37°Cfor30minwith10μLof300μMofSuccinyl-LLVY-AMCand85μLofassaybuffer(20mMTris-HCl,pH7.5,and20%glycerol).ReleaseoffluorescentAMCismeasuredwithaspectrofluorometerat440nmwithanexcitationwavelengthof380nm[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[3]

MG-132isdissolvedinPBStoastorageconcentrationof50μM[3].

C6gliomacellsareseededonto96-wellmicroplates(3×104cells/well)andculturedfor24h.ThecellsaretreatedwithPBSorMG-132finalconcentrationsof10,20,30,and40μM,respectively.CellviabilityisassessedusinganMTTassayat3,6,12,and24hafterMG-132treatment.Theabsorbancevalueat570nmisreadusinganautomaticmulti-wellspectrophotometer.C6gliomacells(3×105cells/well)areallowedtogrowoncoverslipsin6-wellcultureplatesfor24h.ThecellsarethentreatedwitheitherPBS(control)or18.5μMMG-132at37°Cfor24h.Cellsgrowingonglasscoverslipsarefixedinmethanolfor5minatroomtemperature.ThefixedcellsarewashedtwicewithPBSandthenincubatedwithHoechst33342for5minatroomtemperatureandobservedunderafluorescencemicroscope.Fragmentedorcondensednucleiarescoredasapoptotic[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[4][5]

MG-132isdissolvedinvehicle(saline)(Mice)[4].
MG-132isdissolvedinvehicle(0.1%DMSO)(Rat)[5].

Mice[4]
C.B-17/lcr-scid/scidJclmiceareinoculateds.c.withHeLa,CaSki,orC33A(1×107cells).Tumorsareallowedtogrowfor1week.Micearekilledandtumorsareremoved.Tumorsarethencutinto2-mmdiameterpiecesands.c.transplantedinC.B-17/lcr-scid/scidJclmice(n=6pergroup).Oneweekafterinoculation,micearetreatedwithi.v.injectionofsaline(control),MG-132(1mg/kg/dose)twiceaweekfor4weeks.Thevolume(V)oftumorsismeasuredbeforeeveryinjection,asestimatedusingequationV=a×b2/2whereaandbaremajorandminoraxesofthetumormeasuredbyacaliper,respectively.
Rat[5]
MaleSprague-Dawleyrats(8weeksold,180-230g)areusedtoestablishpressure-overloadmodel.Allanimalsareseparatedintofourgroups(10ratspergroup):(i)vehicle-treatedshamgroup;(ii)MG-132-treatedshamgroup;(iii)vehicle-treatedabdominalaorticbanding(AAB)group;and(iv)MG-132-treatedAABgroup.Underintraperitonealpentobarbital(50mg/kg)anesthesia,AABiscreatedusinga5-0suturetiedtwicearoundtheabdominalaortainwhicha21-gaugeneedleisinserted.Theneedleisthenretractedyieldinga70-80%constrictionwithanouteraorticdiameterof~0.8mm.Intheshamsurgeryrats,thesamesurgeryisperformedexcepttheaortaisconstricted.AtDay3afterthesurgery,MG-132-treatedratsareintraperitoneallyinjectedwith0.1mg/kg/dayofMG-132for8weeks.Allcontrolanimalsareinjectedwithacorrespondingvolumeofvehicleonly(0.1%DMSO).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].BraunHA,etal.Tripeptidemimeticsinhibitthe20Sproteasomebycovalentbondingtotheactivethreonines.JBiolChem.2005Aug5;280(31):28394-401.

    [2].HanYH,etal.TheeffectofMG132,aproteasomeinhibitoronHeLacellsinrelationtocellgrowth,reactiveoxygenspeciesandGSH.OncolRep.2009Jul;22(1):215-21.

    [3].FanWH,etal.ProteasomeinhibitorMG-132inducesC6gliomacellapoptosisviaoxidativestress.ActaPharmacolSin.2011May;32(5):619-25.

    [4].MatsumotoY,etal.EnhancedefficacyagainstcervicalcarcinomasthroughpolymericmicellesphysicallyincorporatingtheproteasomeinhibitorMG132.CancerSci.2016Jun;107(6):773-81.

    [5].ChenB,etal.MG132,aproteasomeinhibitor,attenuatespressure-overload-inducedcardiachypertrophyinratsbymodulationofmitogen-activatedproteinkinasesignals.ActaBiochimBiophysSin(Shanghai).2010Apr;42(4):253-8.

MolecularWeight

475.62

Formula

C₂₆H₄₁N₃O₅

CASNo.

133407-82-6

Storage

4°C,protectfromlight

Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

10mMinDMSO

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

Purity:>98.0%