XMU-MP-10-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEXMU-MP-10Cat.No.:HY-179570CASNo.:2251132-02-0分⼦式:C₁₈H₁₄BrN₅O分⼦量:396.24作⽤靶点:E1/E2/E3Enzyme作⽤通路:MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性XMU-MP-10⼀种NEDD4抑制剂(KD为43.92nM)。XMU-MP-10能选择性抑制NEDD4的⾃⾝泛素化，同时不响其他泛素化活性。XMU-MP-10能上调β-TrCP并导致YAP降解，且不改变NEDD4的蛋⽩表达⽔平。XMU-MP-10通过增强CD8+T细胞浸润，在体内表现出显著抑制三性乳腺癌肿瘤⽣长的功效。XMU-MP-10通过β-TrCP/YAP/ECM轴增强抗肿瘤免疫反应。XMU-MP-10可⽤于三性乳腺癌的相关研究[1]。体外研究XMU-MP-10interactswiththeHECTdomainofNEDD4atresiduesY604,Y605,andY634[1].XMU-MP-10(0.1-10000μM)bindsspecificallytoWTNEDD4,butnottoNEDD4mutantsatY604A,Y605A,orY634A[1].XMU-MP-10(0.25-10μM,1-12h)significantlyinhibitsthepolyubiquitinationofNEDD4inadose-dependentmanner,upregulatesofβ-TrCPandresultsYAPdegradationinadoseandtime-dependentmannerwithoutaffectingNEDD4proteinexpressioninEMT6,4T1,MDA-MB-231andHCC38cells[1].XMU-MP-10(2-10μM,4h)selectivelyinhibitsNEDD4auto-ubiquitinationwithoutaffectingtheubiquitinationactivityoftheothertestedE3ligasesinHEK-293Tcell[1].WesternBlotAnalysis[1]CellLine:EMT6,4T1,MDA-MB-231andHCC38Concentration:1,2,5and10μMIncubationTime:1,4,8,12hResult:InducedYAPdegradationinadose-dependentmannerbyupregulatingβ-TrCPinmurineTNBCtumorcells.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEInducedYAPdegradationin4T1cellsinatime-dependentmannerbyup-regulatingβ-TrCP.InducedYAPdegradationinadose-dependentmannerbyupregulatingβ-TrCPinhumanTNBCtumorcells.WesternBlotAnalysis[1]CellLine:HEK-293TcellConcentration:2,5and10μMIncubationTime:4hResult:ReducedNEDD4proteinexpression,butE3ligasesfromC2-WW-HECTsubfamily,includingNEDD4L,NEDL1,NEDL2,Smurf1,Smurf2,WWP1,WWP2,andITCH.体内研究XMU-MP-10(25mg/kg,i.v.,dailyfor14days)iswelltoleratedin4T1cellsinduced-BALB/cmicebutnotin4T1cells-inducedBALB/c-numice[1].XMU-MP-10(25mg/kg,i.v.,dailyfor14days)hasacrucialroleforCD8+Tcellsintumorinhibitionandinfluencestheβ-TrCP-YAP-ECMaxisinEMT6cellsinduced-BALB/cmice[1].XMU-MP-10(25mg/kg,i.v.,dailyfor14days)enhancesantitumorimmuneresponsebyincreasingintratumoralinfiltrationofCD8cytotoxicTcellsinahumanizedimmunesystemmicemode[1].AnimalModel:4T1cells(2.5×105suspendedin100μLPBS,i.v.)induced-femaleBALB/cmice(7to9weeks)orfemaleBALB/c-numice(7to9weeks)[1]Dosage:25mg/kgAdministration:i.v.,dailyfor14daysResult:Showedthestablebodyweight;preservedbloodparameters;liver,kidney,andheartfunctions;andunchangedH&Estainingofmajororgans.Significantlyinhibitedtumorgrowthandreducedtumorweight.Observednosubstantialtherapeuticeffectinimmunodeficienthosts.AnimalModel:EMT6(2×105suspendedin100μLPBS,i.v.)induced-femaleBALB/cmice(7to9weeks)[1]Dosage:25mg/kgAdministration:i.v.,dailyfor14daysResult:IncreasedintratumoralinfiltrationofCD8+Tcellsinimmunocompetenthosts.ObservedthedecreaseinYAPlevelsandupregulationofβ-TrCP.DecreasedtheECMformationrelatedproteinsandSiriusredstainedcollagen2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEdeposition.AnimalModel:WildtypeMDA-MB-231(3×106)cellsinducedhuPBMC-NCGmice(8weeks)Dosage:25mg/kgAdministration:i.v.,dailyfor14daysResult:SignificantlyreducedtheTNBCtumorgrowth.SignificantlyincreasedintratumoralCD8+Tcellinfiltrationandreducedcollagendeposition.REFERENCES[1].SuN,etal,.InhibitingNEDD4intriple-negativebreastcancercellsreprogramstumorimmunemicroenvironmentviatheβ-TrCP/YAP/ECMaxis.CellRepMed.2025Oct21;6(10):102420.McePdfHeightCauti