APE1-IN-2-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAPE1-IN-2Cat.No.:HY-151883分⼦式:C₉H₁₂Cl₂N₄O₅Pt分⼦量:522.21作⽤靶点:Apoptosis;MDM-2/p53作⽤通路:Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性APE1-IN-2(compoundAP1)⼀种Pt(IV)前药，靶向⼀个关键的BER蛋⽩，⽆嘌呤/⽆嘧啶核酸内切酶1(APE1)。APE1-IN-2具有抗癌活性。APE1-IN-2可诱导细胞内铂积累，激活DNA损伤反应和凋亡(apoptosis)信号。体外研究APE1-IN-2(compoundAP1)canstronglyinhibitthegrowthofmalignantcells,includingCisplatin-resistantcancercells,withupto18.11timesinhibitioncomparedwithCisplatin(HY-17394)[1].APE1-IN-2(500nM,24h)arreststhecellcycleinA549andMCF7cells[1].APE1-IN-2(10μM,24h)inducesp53-dependentapoptosisinA549cells[1].APE1-IN-2(0-250μM,72h)inhibitsAP-cuttingactivitywithanIC50of45.14±17.37μM[1].APE1-IN-2candirectlyinhibittheAPendonucleaseactivityofAPE1,leadingtoaninterruptionofmiRNAprocessingandupregulationofthetumorsuppressorPTEN[1].CellProliferationAssay[1]CellLine:A549(non-smallcelllungcancer),MCF7(breastcancer),U251(glioblastoma),A375(melanoma),PC3(prostatecancer),andHEP-G2(hepatocarcinoma)celllinesConcentration:IncubationTime:72hResult:DemonstratedmorepotentantiproliferationeffectsthanCisplatin(HY-17394),withIC50of0.45±0.03,0.43±0.03,4.70±0.14,0.39±0.03,5.65±0.21,and3.53±0.31μMinA549,MCF7,U251,A375,PC3,andHEP-G2celllines,respectively.CellCycleAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:A549andMCF7cellsConcentration:500nMIncubationTime:24hResult:InducedthemostsevereS-phasearrestinA549andMCF7cells.CellProliferationAssay[1]CellLine:A549cellsConcentration:10μMIncubationTime:24hResult:Causedapoptosisinapproximately38.7%(22.9%earlyapoptosisand15.8%lateapoptosis)ofcancercells.WesternBlotAnalysis[1]CellLine:A549andHEK-293TcelllinesConcentration:0,16,40,100,250μMIncubationTime:72hResult:Significantlyincreasedthelevelofp53by2.09±0.51-fold.Slightlyraisedthelevelsofp53,γH2A.X,andcl.PARPinHEK-293T.InhibitedAP-cuttingactivitywithanIC50valueof45.14±17.37μM.体内研究APE1-IN-2(compoundAP1)(2mg/kg,IP,onceevery3daysfor15days)exhibitsanantitumoreffectontheA549xenograftmodel[1].AnimalModel:BALB/cnudemice(5week-old,female,16±2gofbodyweightbearingA549xenografttumors)[1]Dosage:2mg/kgAdministration:IP,onceevery3daysfor15daysResult:Exhibiteda3.86-foldxenografttumorinhibitoryactivitycomparedtoCisplatin.Didnotsignificantlyalterthebodyweightofmice,improvingitssufficientsafety.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].YuanY,etal.Pt(IV)ProdrugasaPotentialAntitumorAgentwithAPE1InhibitoryActivity.JMedChem.2022Nov24;65(22):15344-15357.McePdfHeightCaution:Producthasnotbeenfullyvalidatedform