SU212-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESU212Cat.No.:HY-179578CASNo.:1262219-89-5分⼦式:C₂₅H₂₇NO₆分⼦量:437.48作⽤靶点:Enolase;AMPK;Autophagy;Apoptosis;mTOR;Caspase作⽤通路:MetabolicEnzyme/Protease;Epigenetics;PI3K/Akt/mTOR;Autophagy;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SU212⼀种⿁⾅毒素衍⽣的ENO1抑制剂以及AMPK激活剂。SU212能选择性诱导细胞的氧化磷酸化、降低肿瘤细胞的糖酵解活性和葡萄糖摄取、并且直接结合ENO1同时不响正常细胞中的通路。SU212可以诱导凋亡(apoptotic)并且通过蛋⽩酶体和⾃噬(autophagic)途径诱导ENO1降解但不抑制其催化活性。SU212通过激活AMPK(不依赖于能量应激，也不受⾎糖或胰岛素状态响)，导致三乳腺癌细胞发⽣M期阻滞和凋亡(apoptotic)在体外表现出强效的抗肿瘤活性。SU212在同系、异种移植和糖尿病⼩⿏模型中抑制肿瘤⽣长和转移，具有优异的安全性特征。SU212可⽤于TNBC，糖尿病和脂肝研究[1][2]。体外研究SU212(0.01-850μM,48h)demonstrateslowertoxicityandhigherpotencyagainstTNBCcells(MDA-MB-231)thanEtoposidewithanIC50of0.26μM;inhibits50%cellviabilityinhumanTNBCcellswithIC50svaluesof0.1,0.24,and0.037μMforMDA-MB-468,SUM159,andBT549respectively,andinmouseTNBCcelllineswithIC50valuesof0.85,0.18,0.039,and0.31μMfor4T1,EMT6,E0771,andPY8119[1][2].SU212(0.5μM,6h)hasadifferenttargetthanEtoposideinMDA-MB-231cellsandpromotesENO1degradationthroughbothproteasomalandautophagicpathways;thiseffectispartiallyblockedbyco-treatmentwithMG132or3MA[1].SU212(0.1-10μM,3min-6h)increasesthethermalstabilityofbothENO1andENO3andstrongerinteractionwithENO1cellsandexhibitsadose-dependentinmultipleTNBCcelllines(MDA-MB-231,MDA-MB-468,andEMT6[1].SU212(0.25or0.5μM,1.5h)inhibitstheoveralloxygenconsumptionrate,extracellularacidificationrate,andglycolyticrateinMDA-MB-231,MCF12A,andHEK293cells,withoutaffectingtheglycolyticrateorviabilityofnormalcells[1].SU212(0.1-0.5μM,6-10days)inhibitstheclonogenicpotential,reflectingthesuppressionoftumorregenerationandrecurrence,inTNBCcells[1].1/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESU212(0.1-0.5μM,6or12h)inducesG2-/M-phasearrestinMDA-MB-468andMDA-MB-231[2].SU212(0.5μM,12h)decreasestheabundancesofdifferentformsoftubulininMCF10AandMCF12AorTNBCMDA-MB-231andMDA-MB-468celllines[2].SU212(0.25or0.5μM,12-48h)induces12-60%apoptoticcelldeathbutnotautophagiccelldeathinMDA-MB-468,MDA-MB-231[2].SU212(0.25or0.5μM,1h-6h)activatesAMPKviaphosphorylationofAMPKαatThr172inMDA-MB-231cellandinducesrobustactivationofAMPKαinMDA-MB-468,MDA-MB-231[2].SU212(0.25μM-0.5μM,30min-6h)inhibitslactateproductionanddecreasesthecellularinMDA-MB-468andMDA-MB-231,notaffectthecellularlevelofD-glucose,glucose-6-phosphate/fructose-6-phosphate,ATP,citrate,OCRandECARα-ketoglutarateinMDA-MB-231cells[2].SU212(0.5μM,12h)significantlyincreasesinthelevelsofproteinsassociatedwithoxidativephosphorylation,decreasesthelevelsofproteinsassociatedwithglycolysisandthepentosephosphatepathwayinMDA-MB-231andMDA-MB-468celllinesbutnotinnormalbreastcelllines[2].SU212(0.1-0.5μM,6or72h)hascytotoxiceffectthatdependentonAMPKactivationinMDA-MB-468andMDA-MB-231[2].SU212(0.2-0.6μM,48h)activatesAMPKindependentofenergystressinTNBCcelllines[2].WesternBlotAnalysis[1]CellLine:MDA-MB-231andEMT6Concentration:0.1μMIncubationTime:6hResult:Significantlyalteredthesubcellularlocalizationofeno1,mostsubstantiallylimitingthemembrane-boundpool,whileexertingmorelimitedeffectsonitsnuclearandmitochondrialpools.Inducedinhibitionofeno1localizationtothecellmembranewaspartiallyreversedbyco-treatmentwithMG132and3MA.WesternBlotAnalysis[1]CellLine:MDA-MB-231cellsConcentration:0.5μMIncubationTime:6hResult:DidnotstabilizesTOP2A.InducedENO1degradation,andthiseffectwaspartiallyrescuedbyco-treatmentwitheitherMG132or3MA.WesternBlotAnalysis[1]CellLine:MDAMB-231,MDA-MB-468,andEMT62/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:6hIncubationTime:6or12hResult:StronglyinhibitedENO1proteinexpression,doesnotchangeENO3proteinexpression.CellProliferationAssay[1]CellLine:MDA-MB-231,MDA-MB-468,SUM159andBT549,4T1,EMT6,E0771andPY8119Concentration:0.1,0.25and0.5μMIncubationTime:6-10daysResult:SignificantlyinhibitedTNBCcells’clonogenicpotentialandeightothercancertypes.CellCycleAnalysis[2]CellLine:MDA-MB-468andMDA-MB-231Concentration:0.1,0.25and0.5μMIncubationTime:6or12hResult:Increasedthesub-g1phase(20-35%)with6h.Inducedmitoticphasearrest(20-31%)with6h.WesternBlotAnalysis[2]CellLine:MDA-MB-468andMDA-MB-231Concentration:0.5μMIncubationTime:6hResult:ResultedinthedownregulationofcyclinB1andCDK1expression,andanincreaseintheexpressionofphospho-histoneH3.WesternBlotAnalysis[2]CellLine:MDA-MB-468andMDA-MB-231Concentration:0.5μMIncubationTime:12hResult:CleavedPARP,Bax,Bcl-2andCC.Inducedpro-apoptoticBaxexpressionandinhibitedBcl-2expression,leadingtoasignificantincreaseinBax/Bcl-2ratio.3/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEInducedthecleavageofPARPandcaspase3.InhibitedBeclin-1butdidnotaffectLC3A/B.WesternBlotAnalysis[2]CellLine:MDA-MB-468,MDA-MB-231Concentration:0.5μMIncubationTime:6hResult:Downregulatedofmtorandacetyl-coacarboxylase(ACC)inhibition.WesternBlotAnalysis[2]CellLine:Dorsomorphin(HY-13418A)pretreatedMDA-MB-468andMDA-MB-231.Concentration:0.5μMIncubationTime:6hResult:DidnotinduceAMPKWerehealthierandhadamorphologysimilar.CellViabilityAssay[2]CellLine:DorsomorphinpretreatedMDA-MB-468andMDA-MB-231Concentration:0.5μMIncubationTime:72hResult:RevertedcytotoxiceffectbyDorsomorphinfrom73%to86%.CellViabilityAssay[2]CellLine:MDA-MB-468Concentration:0.2,0.4and0.6μMIncubationTime:48hResult:Producedanadditiveinhibitoryeffectinhypoglycaemicconditions,resultinginabout20–30%enhancedinhibition(Pꢀ<ꢀ0.05)relativetohyperglycaemicconditions.DidnotaffectthecytotoxicityofMDA-MB-468cellsbyinsulin.Maintainedconsistentcytotoxicityacrossphysiologicalandhighinsulinlevels(1–100ꢀng/ml)butmodestlyreduced(by17%)atasupra-pharmacologicalconcentration(10,000ꢀng/ml).4/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究SU212(30mg/kg,i.p.,oncedailyfor3days)reducescellularglycolyticrate,loweringtheoverallglucosedemandoftumorcellsinMDA-MB-231cellsinduced-femaleNSGmice[1].SU212(100-400mg/kg,i.p.,once)haswelltoleranceininfemaleC57BL/6miceandSDrats[1].SU212(30mg/kg,i.p.5daysaweekfor21daysor24days)notinduceliverorkidneytoxicityinsyngeneicorthotopicTNBCmodels[1].SU212(20mg/kg,i.p.,fivedaysaweek)haspositiveeffectontumordevelopmentandprogressioninhemizygousMMTV-PyMTtransgenicfemalemousemodel[1].SU212(30mg/kg,i.p.,5days/weekfor21days)leadstoalteredsubcellularlocalizationandimpairedmoonlightingfunctionsbyinducingthedegradationofENO1inorthotopicEMT6mousemodelofTNBC[1].SU212(10mg/kg,i.p.,5days/weekfor32days)restrainstumorgrowthinhyperglycemicandhyperinsulinemicconditionsandmayhelpimprovediabeticandfattyliverconditionsinLeprdb(Db/Db)mousemodel[1].SU212(15or30mg/kg,i.p.,21days)inhibitstumourprogressioninluciferase-labelledMDA-MB-231xenograftmousemodel[2].SU212(30mg/kg,i.p.,30days)inhibitslungmetastasisintail-veinlung-metastasismousemodel[2].SU212(30mg/kg,i.p.,21days)demonstratespotentantitumorgrowthandanti-metastaticactivitybyactivatingtheAMPKpathwaywithnosignificantbodyweightlossorhepatorenaltoxicity,improveslipidmetabolismin4T1syngeneicmousexenograft[2].AnimalModel:MDA-MB-231cellsinduced-femaleNSGmice(8-9weeks)[1]Dosage:30mg/kgAdministration:i.p.,oncedailyfor3daysResult:Didnotsignificantlyreducetumorsizecomparedtothecontrol.Significantlyreducedfdguptakebytumorcells.AnimalModel:FemaleC57BL/6miceandSDrats[1]Dosage:100,200,and400mg/kgAdministration:i.p.,onceResult:Observednosignsofstress(behavioral,neurological,andautonomicstresses.Didnotobserveanysignificantweightlossormortality.AnimalModel:EMT6cells(1x105)induced-Balb/cmiceandPY8119induced-C57BL/6mice[1]Dosage:30mg/kgAdministration:i.p.5daysaweekfor21days(EMT6induced-Balb/cmice)or24days(PY8119induced-C57BL/6mice)Result:SignificantlydelayedtumorgrowthinbothTNBCmodels,resultinginsignificantlylower5/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEtumorweightatexperimentend.DidnotcausedanysignificantchangesinthesemarkersofliverornephrotoxicityinC57BL/6micebearingPY8119tumors.AnimalModel:EMT6cells(1x105)induced-femaleNSGmice[1]Dosage:30mg/kgAdministration:i.p.,5days/weekfor21daysResult:Reduced66%lungmetastasis.AnimalModel:FemaleFVB/N-Tg(MMTV-PyVT)634Mul/Jmice(5-6weeks)[1]Dosage:20mg/kgAdministration:i.p.,fivedaysaweekResult:Improvedoverallsurvivalandreducedtumorburdenandincidence.AnimalModel:PY8119cells(1x105)induced-femaleDb/Dbmice(10weeksold)[2]Dosage:10mg/kgAdministration:i.p.,5days/weekfor32daysResult:Reducedtumorgrowth.Reducedoveralltumorburden.Inhibitseno1expression.Didnotsignificantlyaffectoverallmousebodyweight.Didcauseasignificantdropinbloodglucoselevel.SignificantlyreducesthelevelofAST,ALT,alkalinephosphataseandglutamatedehydrogenase(GLDH).Significantlyreducedliverweight.Reducedfat-associatedspaceby80%-90%.Resultedinadistinctmrnaprofile,characterizedbythedownregulationofpi3kpathwaygenesandtheupregulationofmitochondrialrespirationpathwaygenes.AnimalModel:MDA-MB-231cells(2×106)induced-femaleNOD/SCIDmice(7-8weeks)[2]Dosage:15and30mg/kgAdministration:i.p.,21daysResult:InhibitedTNBCtumourgrowthby46and71%,respectively.6/7MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDidnotshowsignificantbody-weightchangesandnostressorpainbehaviour.Had42and81%lesstumourweightat15mg/kgand30mg/kgdosesrespectively.AnimalModel:MDA-MB-231cells(1×106)induced-femaleNOD/SCIDmice(6-7weeks)[2]Dosage:30mg/kgAdministration:i.p.,everydayfor4weeksResult:Reducedthenumberofmetastaticfociinthelungby69%.AnimalModel:4T1cells(5×105)induced-femaleBalb/cmice(7-8wee