Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEATR/PARP1-IN-1Cat.No.:HY-174828分子式:C??H??FN??O?分子量:820.87作用靶點:PARP;ATM/ATR;Apoptosis作用通路:CellCycle/DNADamage;Epigenetics;PI3K/Akt/mTOR;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性ATR/PARP1-IN-1是一種ATR/PARP1雙重抑制劑，對ATR的IC50為17.3nM，對PARP1的IC50為0.38nM。ATR/PARP1-IN-1能有效降低細胞活力，誘導細胞凋亡(apoptosis)和DNA損傷。ATR/PARP1-IN-1在三陰性乳腺癌(TNBC)模型中顯著抑制了集落形成、遷移和侵襲。ATR/PARP1-IN-1在MDA-MB-468移植瘤小鼠模型中有效抑制了腫瘤生長，且未引起顯著體重變化[1]。IC50&TargetPARP1PARP2TNKS1TNKS20.38nM(IC50)5.1nM(IC50)116nM(IC50)740.5nM(IC50)PARP7ATMATRPI3Kα28.5nM(IC50)＞5000nM(IC50)17.3nM(IC50)＞2500nM(IC50)DNA-PK＞5000nM(IC50)體外研究ATR/PARP1-IN-1(CompoundB8)showsanti-proliferationactivityinTNBCcellswithIC50sof1.89μM(MDA-MB-231),0.32μM(MDA-MB-468),0.009μM(MDA-MB-436)[1].ATR/PARP1-IN-1(0.5-1μM,48h)inducesG2/McellcyclearrestinMDA-MB-231cellsandMDA-MB-468cells,withasignificantlystrongereffectthanthecombinationofCeralasertib(AZD6738)(HY-19323)andOlaparib(HY-10162)[1].ATR/PARP1-IN-1(0.5-1μM,72h)demonstratesamarkedlystrongercapacitytoinduceapoptosisthanthecombinationofAZD6738andOlaparibinMDA-MB-231andMDA-MB-468cellsasdeterminedbyAnnexinV/PIstainingassay[1].ATR/PARP1-IN-1(0.5-1μM,10days)exhibitsasignificantlygreaterinhibitoryeffectonthecolonyformationrate,migration,andinvasioninbothMDA-MB-231andMDA-MB-468cellscomparedtoeithertreatmentof1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAZD6738orOlaparibadministeredalone,ortheircombination[1].ATR/PARP1-IN-1(1-2μM,48h)interfereswiththeEpithelial-mesenchymaltransition(EMT)ofMDA-MB-468cells[1].ATR/PARP1-IN-1(0.5-1μM,48h)inducessignificantDNAdamageinMDA-MB-231cellsandMDA-MB-468cells[1].ATR/PARP1-IN-1(1-2μM,48h)suppressesCHK1phosphorylationthroughATRinhibitioninMDA-MB-468cells[1].CellCycleAnalysis[1]CellLine:MDA-MB-231cellsandMDA-MB-468cellsConcentration:0.5,1μMIncubationTime:48hResult:InducedG2/McellcyclearrestinMDA-MB-231cellsandMDA-MB-468cells.ApoptosisAnalysis[1]CellLine:MDA-MB-231cellsandMDA-MB-468cellsConcentration:0.5,1μMIncubationTime:72hResult:InducedapoptosisinMDA-MB-231cellsandMDA-MB-468cells.Immunofluorescence[1]CellLine:MDA-MB-231cellsandMDA-MB-468cellsConcentration:0.5,1μMIncubationTime:48hResult:IncreasedtailintensitymoremarkedlythanAZD6738,Olaparib,andtheircombinationtreatment.IncreasedtheformationofγH2AX.WesternBlotAnalysis[1]CellLine:MDA-MB-468cellsConcentration:1,2μMIncubationTime:48hResult:DecreasedtheproteinexpressionofBCL-2.InducedmoreBAXandcleaved-caspase-3proteinexpressioncomparedtothe2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEcombinationofAZD6738andOlaparib.IncreasedtheexpressionoftheepithelialcellmarkerE-cadherin.DecreasedtheexpressionofthemesenchymalcellmarkerVimentin.ReducedtheproteinlevelsofbothATRandPARP1.IncreasedtheDSBmarkerγH2AX.DecreasedCHK1Ser345phosphorylation.EnhancedCDK1Tyr15phosphorylation.體內研究ATR/PARP1-IN-1(25-50mg/kg,i.p.,bisindiefor28days)exertsgoodantitumorefficacyandpossessesafavorablesafetyprofileinMDA-MB-468xenograftedmicemodel[1].AnimalModel:FemalenudemiceweresubcutaneouslywithMDA-MB-468cells(1x107)[1]Dosage:25,50mg/kgAdministration:i.p.dailyfor28daysResult:SuppressedthegrowthofMDA-MB-468xenograftedmice.DecreasedKi67expressionandincreasedγH2AXandcleaved-caspase-3expression.Showednosignificanteffectonbodyweight.Didnotcausesignificantchangesinorganstructureorcellularmorphologyofheart,liver,spleen,lungs,andkidneys.REFERENCESGaoY,etal.NovelATR/PARP1DualInhibitorsDemonstrateSynergisticAntitumorEfficacyinTriple-NegativeBreastCancerModels.AdvSci(Weinh).2025Jun16:e01916.McePdfHe