Pro-PEG3-BA-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPro-PEG3-BACat.No.:HY-180965CASNo.:3057939-64-4分⼦式:C₃₇H₅₂ClN₈O₇P分⼦量:787.28作⽤靶点:PROTACs;Anaplasticlymphomakinase(ALK);EGFR;Apoptosis作⽤通路:PROTAC;ProteinTyrosineKinase/RTK;JAK/STATSignaling;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Pro-PEG3-BA⼀种靶向EML4-ALK/EGFR的PROTAC降解剂，可分别以DC50为0.42μM和13.50μM降解EML4-ALK与EGFR突变体(L858R/T790M)。Pro-PEG3-BA在体外实验中能够抑制⾮⼩细胞肺癌细胞的增殖，并诱导细胞发⽣周期阻滞与凋亡(apoptosis)。Pro-PEG3-BA具有良好的安全性特征，且在体内实验中可通过重新调控泛素-蛋⽩酶体系统降低EML4-ALK蛋⽩的表达⽔平。Pro-PEG3-BA具备⽤于⾮⼩细胞肺癌的研究[1][2][3]。体外研究Pro-PEG3-BA(0-50min)bindstopurifiedALKwithaKdof387nMinvitro[2].Pro-PEG3-BAbindsGID4proteinwithKdvalueof6.05μMinHEK293Tcells[3].Pro-PEG3-BA(0-20μM,48h)specificallydegradestEML4ALKfusioninH3122(EML4-ALK),withnoeffectonwildtypeormutantALK[3].Pro-PEG3-BA(48-72h)inhibitsH3122cells(48h)prolifetionwithanIC50valueof0.16μM,inhibitsH1975cells(EGFR-L858R/T790M)(72h)prolifetionwithanIC50valueof8.80μM[3].Pro-PEG3-BA(48-72h)inhibitscellgrowthwithanIC50valueof0.16μMforH3122(EML4-ALK)cells(48h),and8.8μMforH1975(EGFR-L858R/T790M)(72h)cells,withlittletoxicitytonormalcells(HEK293Tcells)[3].Pro-PEG3-BA(10μM,24h)dramaticallydownregulatesALKproteinabundancealongsideCD2AP,MRPS23,RNF2,RAB18andTRMT10C,demonstratinghighselectivityintargetingALKfordegradation;concurrently,itupregulatesPOLR2F,WASHC2C,NCOR2,ZNF622,ALDH6A1,PRRC1,GPD1L,EXOC7,WACPAF1inH1975(EGFRL858R/T790M)cells[3].Pro-PEG3-BA(10-20μM,0-24h)inducestheapparentreductionofEML4-ALKorEGFRmutantproteinsinatime-dependentmannerinH3122(EML4-ALK)cells(10μM)andH1975(EGFR-L858R/T790M)cells(20μM)[3].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEPro-PEG3-BA(0.5-20μM,6or12h)reducesthelevelsofEML4-ALKandEGFRmutantsinaproteasome-dependentmannerinH3122(EML4-ALK)andH1975(EGFR-L858R/T790M)cells[3].Pro-PEG3-BA(5-10μM,48-72h)inducescellcyclearrestandapoptosisinH1975(EGFR-L858R/T790M)cellsandH3122(EML4-ALK)cells[3].WesternBlotAnalysis[3]CellLine:H3122cells(EML4-ALK),SK-N-BE(2)(expresswildtypeALK,andSH-SY5Y)andSH-SY5Y(harborstheALK-F1174L)Concentration:0,0.01,0.1,1,10and20μMIncubationTime:48hResult:LedtoanoticeabledownregulationoftheEML4-ALKproteininH3122(EML4-ALK)cells.Didnotaffecttheproteinlevelsofeitherwild-typeormutantALK.WesternBlotAnalysis[3]CellLine:H3122cells(EML4-ALK)andH1975(EGFRL858R/T790M)cellsConcentration:0.5or20μMIncubationTime:6hand12hResult:MediatedthedegradationofEML4-ALKorEGFRmutant,whichwasblockedbytheproteasomeinhibitorMG132(HY-13259)(10μM)insteadoflysosomeinhibitorChloroquine(HY-17589A)(25μM).WesternBlotAnalysis[3]CellLine:H3122(10μM)andH1975(20μM)Concentration:H3122(10μM)andH1975(20μM)IncubationTime:0,12,24,36,48and72hResult:InducedtheapparentreductionofEML4-ALKorEGFRmutantproteins,witheffectsobservedaround45minand12h.CellCycleAnalysis[3]CellLine:H3122cells(EML4-ALK)andH1975(EGFRL858R/T790M)cellsConcentration:5or10μMIncubationTime:48(forH3122cells)or72h(forH1975cells)Result:InducedanaccumulationofcellsintheG1phaseandconcurrentlycausingadecreaseinthenumberofcellsintheSorG2phase.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESignificantlyincreasedtheproportionofbothearlyandlateapoptoticcellsinaconcentration-dependentmanner.体内研究Pro-PEG3-BA(10mg/kg,i.p.,everyotherdayforatotalof8doses)decreasesEML4-ALKexpressionwithsafetyprofileinaH3122cellsinducedxenografttumormicemodel[3].AnimalModel:H3122cellsinduced-femalenudemice[3]Dosage:10mg/kgAdministration:i.p.,everyotherdayforatotalof8dosesResult:Didnotcausesignificantvariationsinthemicebodyweight.DecreasedEML4-ALKproteinlevelsintumors.REFERENCES[1].ChenX,etal.Mightymini-PROTACs:anemergingclassofdegraders.EurJMedChem.2026Jan5;301:118202.[2].ZhangJ,etal.Linker-freePROTACsefficientlyinducethedegradationofoncoproteins.NatCommun.2025May23;16(1):4794.[3].ZhangJ,etal.DistinctAminoAcid-BasedPROTACsTargetOncogenicKinasesforDegradationinNon-SmallCellLungCancer(NSCLC).JMedChem.2024Aug22;