Arg-PEG1-Tαsyn-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEArg-PEG1-TαsynCat.No.:HY-180976分⼦式:C₂₂H₂₉N₇O₂S分⼦量:455.58作⽤靶点:PROTACs;α-synuclein作⽤通路:PROTAC;NeuronalSignaling储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Arg-PEG1-Tαsyn⼀种靶向α-syn的PROTAC降解剂，在U251细胞中其DC50为0.28ꢀμM。Arg-PEG1-Tα-syn采⽤氨酸精氨酸(Arg)作为E3连接酶配体，并采⽤⼀种苯并噻唑-苯胺变体作为靶向α-突触核蛋⽩(α-syn)的弹头。Arg-PEG1-Tαsyn在哺乳动物细胞中对野⽣型α-突触核蛋⽩（α-syn）及其A53T突变体均表现出⾼效的降解效果。Arg-PEG1-Tαsyn在体外通过E3泛素连接酶UBR1显著减少α-syn聚集。在体内，Arg-PEG1-Tαsyn具有良好的安全性，并能显著改多巴胺能神经元损伤和运动功能障碍。Arg-PEG1-Tαsyn可⽤于帕⾦森病的相关研究[1][2]。体外研究Arg-PEG1-Tα-syn(0-10μM,48h)significantlypromotesthereductionofα-synA53TinU251cellswithaDC50of0.28μM,andaDmaxof90.5%at5μM[1].Arg-PEG1-Tα-syn(1μM,0-72h)time-dependentlyexertsα-synA53TdegradationinU251/α-synA53Tcells[1].Arg-PEG1-Tα-syn(1μM,48h)exhibitsconsistentdegradationeffectsonα-syninU251/α-synWT,U251/α-synA53T,293/α-synWT,293/α-synA53T,SH-SY5Y/α-synWTandSH-SY5Y/α-synA53Tcells[1].Arg-PEG1-Tα-syninducesα-synA53Treduction,aneffectthatisreversedbyMG132(HY-13259)butnotbyChloroquine(HY-17589A)[1].Arg-PEG1-Tα-syn(1μM,48h)mediatestheregulationofα-synWTandα-synA53TviatheE3ubiquitinligaseUBR1inU251(knockeddownUBR1,UBR2,UBR4,andUBR5separatelyusingshRNA)cells[1].Arg-PEG1-Tα-syn(0-5μM,48h)protectscellsfromthetoxicityinducedbyα-synWTorα-synA53ToverexpressioninSH-SY5Ycells(overexpressingα-synWTorα-synA53T)byreducingα-synA53Taggregation[1].WesternBlotAnalysis[1]CellLine:U251/α-synA53Tcells1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:1μMIncubationTime:0,12,24,48and72hResult:Degradedtheα-synA53Tasearlyas12h,reachingthepeakat48h.WesternBlotAnalysis[1]CellLine:U251/α-synWT,U251/α-synA53T,293/α-synWT,293/α-synA53T,SH-SY5Y/α-synWTandSH-SY5Y/α-synA53TcellsConcentration:1μMIncubationTime:48hResult:Triggeredefficientreductionofα-synWTorα-synA53T.WesternBlotAnalysis[1]CellLine:U251cells(knockeddownUBR1,UBR2,UBR4,andUBR5separatelyusingshRNA)Concentration:1μMIncubationTime:48hResult:Inducedthedegradationofbothα-synA53Tandα-synWTinU251cells,aneffectthatismarkedlysuppressedbyUBR1knockdownbutbarelyaffectedbyUBR2,UBR4,orUBR5knockdown.CellViabilityAssay[1]CellLine:SH-SY5Ycells(overexpressingα-synWTorα-synA53T)Concentration:0,1and5μMIncubationTime:48hResult:Significantlyenhancedcellviabilityinα-synWTcellsat5μMandinα-synA53Tcellsstartingat1μM.Immunofluorescence[1]CellLine:SH-SY5YcellsConcentration:5μMIncubationTime:48hResult:Significantlyreducedα-synA53Taggregates.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEReducedα-synA53Taggregates.体内研究Arg-PEG1-Tα-syn(mixedwithOP50bacteriaatvaryingconcentrationsforfeeding,p.o.,fromtheL1larvalstagetoday-5adulthood)decreasesα-synaggregates,significantlyimprovesthemorphologyofneuronalcellbodiesandsynapsesandpartiallyrestorethedopaminergicneuronalfunctionaldeficitsinducedbyα-synpathologyinC.elegansNL5901[1].Arg-PEG1-Tα-syn(0-10μMweremixedwithOP50bacteriaforfeeding,p.o.,fromtheL1larvalstagetoday-5adulthood)effectivelyameliorateslocomotordysfunctioninducedbyα-synpathologyinadose-dependentmannerinC.elegansoverexpressinghumanα-synA53T.withsafetyprofile(5μM)inC.elegansUM0020andC.elegans(W.T.)[1].AnimalModel:C.elegansUM0020(A537mutant)andC.elegansNL5901(W.T.)[1]Dosage:0,5and10μMAdministration:p.o.,omtheL1larvalstagetoday-5adulthoodResult:SignificantlyrescuedthelocomotordeficitsofUM0020wormsatday-1andday-5ofadulthood,withamorepronouncedeffectatday-5.SignificantlyimprovedthelocomotorperformanceofUM0020wormsat1μM.AnimalModel:C.elegansUM0020andC.elegansNL5901(W.T.)[1]Dosage:5μMAdministration:p.o.,omtheL1larvalstagetoday-5adulthoodResult:Hasnosignificantdifferenceinthrashingfrequency.REFERENCES[1].ShenL,etal.Targeteddegradationofα-synucleinbyarginine-basedPROTACs.JBiolChem.2025Aug;301(8):110449.[2].ChenX,etal.Mightymini-PROTACs:anemergingclassofdegraders.EurJMedChem.2026Jan5;