Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPZL-ACat.No.:HY-174216CASNo.:3068830-89-4分?式:C??H??ClN?O?分?量:368.82作?靶點:DNA/RNASynthesis;OxidativePhosphorylation;MitochondrialMetabolism作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PZL-A線粒體DNA(mtDNA)合成激活劑。PZL-A可恢復突變型聚合酶γ(POLγ)的野?型活性，對A467T和G848S的AC50分別為160nM和20nM。PZL-A可激活細胞內(nèi)的mtDNA合成，增強氧化磷酸化機制的?物合成和細胞呼吸作?。PZL-A有望緩解POLG和其他與線粒體DNA缺失相關的嚴重疾病[1]。體外研究PZL-A(0-100μM,10min)dose-dependentlyactivatesthemutants(R232H,A467T,G848S,andW748S)(AC50:20-200?nM),stabilizestheinteractionwithtemplate,andinteractsdirectlywiththePOLγholoenzymewithincreaseofunfoldingtemperature[1].PZL-A(1μM,0-15min)stimulatesDNAsynthesisandenhancestherateofdNTPincorporationinmutants(R232H,A467T,G848SandW748S)withoutinfluenceonexonucleaseactivityacrossabroadrangeofdNTPconcentrations(0.08-10?μM)[1].PZL-A(10μM)interactingdirectlywiththePOLγholoenzymeandincreasingtheunfoldingtemperatureinmutants(R232H,A467T,G848SandW748S)[1].PZL-AbindstoahydrophobicpocketbetweenPOLγAandPOLγBwithaC-shapedorientation,andthesiteisgenerallyunaffectedbymostdisease-causingmutations[1].PZL-A(10μM,7.5-60min)hasamarkedstimulatoryeffect,leadingtoDNAsynthesisoflongerdouble-strandedDNA(dsDNA)products[1].PZL-A(1-3μM,7-14days)stronglystimulatesmtDNArepopulationrateswithgoodtoleranceinA467T/G848SandW748S/R232Hmutantfibroblastsaswellasquiescentfibroblasts[1].PZL-A(0.00001-10μM,5-10days)dose-dependentlystimulatesfull-lengthmtDNArepopulationandincreases7SDNAlevelsinA467T/G848SandW748S/R232Hmutantfibroblasts[1].PZL-A(0.02-1μM,7-10days)increasesmtDNAlevelsandamelioratesOXPHOSactivityinA467T/G848SandW748S/R232HmutantfibroblastsandG848S/G848SmutantNSCs[1].1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].ValenzuelaS,etal.SmallmoleculesrestoremutantmitochondrialDNApolymeraseactivity.Nature.2025Jun;642(8067):501-507.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuse