Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMOPIPPCat.No.:HY-148114CASNo.:1485521-76-3分?式:C??H??N?O?分?量:320.39作?靶點(diǎn):Others作?通路:Others儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性MOPIPP?種新型吲哚查爾酮、液泡素-1，?種MOMIPP(HY-148114)的?致命液泡誘導(dǎo)2-丙類似物。MOPIPP能誘導(dǎo)細(xì)胞液泡化，增加?噬體數(shù)?。MOPIPP還會引發(fā)細(xì)胞巨泡式死亡(methuosis)，并中斷葡萄糖攝取和糖酵解代謝。MOPIPP能夠透過?腦屏障，對膠質(zhì)母細(xì)胞瘤細(xì)胞有抑制作?。體外研究MOPIPP(10μM;48h)inducescellularvacuolizationbutdoesnotcausecelldeathinU251glioblastomacells，exhibitingcharacteristicsoflateendosomes[1][2].MOPIPP(10μM;24h)resultsanincreasingLC3fluorescenceassociatedwiththenumberofautophagosomesandinhibitsfusionofautophagosomeswithlysosomes[1].MOPIPP(10μM;24h)increasestheamountsofexosomalmarkerproteinsinvesiclefractionsrecoveredfrom293Tcells[2].MOMIPP(10μM;24hand5h,respectively)causesearlydisruptionsofglucoseuptakeandglycolyticmetabolism,inducesmethuosis,aformofnon-apoptoticcelldeath,inglioblastomaandothercancercelllines[3].MOMIPP(10μM;4hand24h)selectivelyactivatestheJNK1/2stresskinasepathway,resultinginphosphorylationofc-Jun,Bcl-2andBcl-xL[3].Immunofluorescence[1]CellLine:U251glioblastomacellsConcentration:10μMIncubationTime:24hours;incubatedwith2.5μg/mlAcridineOrange(HY-101879)for45min1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Causedaccumulationofautophagosomemarkers.IncreasedpunctateLC3fluorescenceandsuggestedanincreaseinthenumberofautophagosomesincells.WesternBlotAnalysis[3]CellLine:U251glioblastomacellsConcentration:10μMIncubationTime:4and24hoursResult:TriggeredincreaseingphosphorylationofBcl-2andBcl-xL,accompaniedtheactivationofJNK.體內(nèi)研究MOMIPP(80mg/kg;i.p.;singledose)readilypenetratesthebloodbrainbarrierinfemaleSwissWebsterMiceand(80mg/kg;i.p.;every24h;15d)iseffectiveinsuppressingprogressionofintracerebralglioblastomaxenograftsinfemaleNCR-Foxn1mice[3].AnimalModel:IntracerebralxenograftmodelinNCR-Foxn1mice(female,7-8weeks,injectedwithU251-LUCcells)[3]Dosage:80mg/kgAdministration:Intraperitonealinjection;every24hoursfor15days;monitoredtumorprogressionbyBLIonthedays7,11,15Result:Significantlyinhibitedtumorprogression.REFERENCES[1].MbahNE,etal.Disruptionofendolysosomaltraffickingpathwaysingliomacellsbymethuosis-inducingindole-basedchalcones.CellBiolToxicol.2017Jun;33(3):263-282.[2].LiZ,etal.Vacuole-inducingcompoundsthatdisruptendolysosomaltraffickingstimulateproductionofexosomesbyglioblastomacells.MolCellBiochem.2018Feb;439(1-2):1-9.[3].LiZ,etal.TheJNKsignalingpathwayplaysakeyroleinmethuosis(non-apoptoticcelldeath)inducedbyMOMIPPinglioblastoma.BMCCancer.2019Jan16;19(1):77.McePdfHeightCaution:Producthasnotbeenfullyvalidate