MG-132-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEMG-132Cat.No.:HY-13259CASNo.:133407-82-6分⼦式:C₂₆H₄₁N₃O₅分⼦量:475.62作⽤靶点:Proteasome;Autophagy;Apoptosis作⽤通路:MetabolicEnzyme/Protease;Autophagy;Apoptosis储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:83.33mg/mL(175.20mM;Needultrasonic)扫描⼆维码，H2O:<0.1mg/mL(insoluble)运⽤溶解⽅案计算器获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1025mL10.5126mL21.0252mL5mM0.4205mL2.1025mL4.2050mL10mM0.2103mL1.0513mL2.1025mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(4.37mM);Clearsolution此⽅案可获得≥2.08mg/mL(4.37mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.08mg/mL(4.37mM);Clearsolution此⽅案可获得≥2.08mg/mL(4.37mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性MG-132(Z-Leu-Leu-Leu-al)⼀种有效的，可逆的蛋⽩酶体(proteasome)抑制剂，IC50为100nM。MG-132有效阻断26S蛋⽩酶体复合物的蛋⽩⽔解活性。MG-132⼀种肽醛，⾃噬(autophagy)激活剂。MG-132还诱导凋亡(apoptosis)[2]。IC50&TargetIC50:100nM(Proteasome),1.2μM(Calpain)[1][3]体外研究MG-132(Z-Leu-Leu-Leu-al)initiatesneuriteoutgrowthinPC12cellsatalowconcentration(30nM)andisaverystronginhibitorof20Sproteasome[3].MG-132(10μM;1hour)reversestheeffectsofTNF-αonIκBdegradationandNF-κBactivationinA549cells[4].MG-132(0.75-5μM;24hours)potentlyinducesp53-dependentapoptosisinKIM-2cellsby26Sproteasomeinhibition[5].MG-132(10-40μM;24hours)significantlyreducestheviabilityofC6gliomacellsinbothtime-andconcentration-dependentmannersandshowstheIC50of18.5μMat24hours[6].MG-132(18.5μM;24hours)inducesdown-regulationofanti-apoptoticproteinsBcl-2andXIAPandup-regulatesexpressionofpro-apoptoticproteinBaxandcaspase-3[6].CellViabilityAssay[3]CellLine:C6gliomacellsConcentration:10,20,30,40μMIncubationTime:24hoursResult:SignificantlyreducedtheviabilityofC6gliomacellsbeginningat6hinbothtime-andconcentration-dependentmannersandshowedtheIC50of18.5μMat24hours.WesternBlotAnalysis[3]CellLine:A549cellsConcentration:10μMIncubationTime:1hourResult:ReversedtheeffectsofTNF-αonIκBdegradationandresultedinareversalofTNF-α-inducedNF-κBactivation.2/4www.MedChemEwww.MedChemE体内研究MG132(10mg/kg;i.p.;dailyfor25daysstarting5daysafterEC9706cellsinjection)significantlyinhibitstumorgrowthoftheEC9706xenograftwithoutcausingtoxicitytomice[7].MG-132(1mg/kg;i.v.;twiceaweekfor4weeks)showspotenttumorinhibitoryeffectagainstmicebearingHeLatumors[8].MG-132(1-10μg/kg/24hours;subcutaneouslyimplantedosmoticpumps;for8days)greatlyincreasestheexpressionlevelsofβ-dystroglycan,α-dystroglycan,α-sarcoglycan,anddystrophininskeletalmusclelysatesinmice(six-month-oldmaleC57BL/10ScSnDMDmdxmice)[9].AnimalModel:5-to6-weeksoldfemaleathymicnudemice(EC9706xenograft)Dosage:10mg/kgAdministration:I.p.;dailyfor25daysstarting5daysafterEC9706cellsinjectionResult:SignificantlyinhibitedtumorgrowthoftheEC9706xenograftwithoutcausingtoxicitytothemice.AnimalModel:Five-week-oldfemaleC.B-17/lcr-scid/scidJclmice(bearingHeLacells)[8]Dosage:1mg/kgAdministration:Intravenousinjection;twiceaweekfor4weeksResult:ThegrowthinhibitionratesinHeLatumorswas49%comparedtothecontrol.户使⽤本产品发表的科研⽂献•Science.2020Dec4;370(6521):eaay2002.•CellMetab.2021Mar26;S1550-4131(21)00113-3.•CellRes.2021Mar;31(3):291-311.•NatCellBiol.2021Mar;23(3):257-267.•Blood.2021Mar18;137(11):1478-1490.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HarhouriK,etal.MG132-inducedprogerinclearanceismediatedbyautophagyactivationandsplicingregulation.EMBOMolMed.2017Sep;9(9):1294-1313.[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):773-81.3/4www.MedChemEwww.MedChemE[5].TsubukiS,etal.Differentialinhibitionofcalpainandproteasomeactivitiesbypeptidylaldehydesofdi-leucineandtri-leucine.JBiochem.1996Mar;119(3):572-6.[6].FiedlerMA,etal.InhibitionofTNF-alpha-inducedNF-kappaBactivationandIL-8releaseinA549cellswiththeproteasomeinhibitorMG-132.AmJRespirCellMolBiol.1998Aug;19(2):259-68.[7].MacLarenAP,etal.p53-dependentapoptosisinducedbyproteasomeinhibitioninmammaryepithelialcells.CellDeathDiffer.2001Mar;8(3):210-8.[8].DangL,etal.ProteasomeinhibitorMG132inhibitstheproliferationandpromotesthecisp