PLK1-BRD4-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPLK1/BRD4-IN-1Cat.No.:HY-143471CASNo.:2412707-81-2分⼦式:C₃₁H₄₃N₉O₂分⼦量:573.73作⽤靶点:Polo-likeKinase(PLK);EpigeneticReaderDomain;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PLK1/BRD4-IN-1(9b)⼀个具有⼝服活性的PLK1和BRD4双重抑制剂，对PLK1和BRD4的IC50值分别为22nM和109nM。PLK1/BRD4-IN-1诱导细胞周期阻滞(cellcyclearrest)和凋亡(apoptosis)，下调⼏种增殖相关癌因的转录，并表现出良好的体内抗肿瘤活性[1]。IC50&TargetBRD4PLK1109nM(IC50)22nM(IC50)体外研究PLK1/BRD4-IN-1(9b)(72h)showsbroad-spectrumantiproliferativeactivities[1].PLK1/BRD4-IN-1(0-9µM,24h)inducescellcyclearrest[1].PLK1/BRD4-IN-1(0-9µM,48h)inducescellapoptosis[1].PLK1/BRD4-IN-1inhibitstheproliferativeofcancercellsbyexertingitsinhibitoryactivityonbothPLK1andBRD4[1].CellViabilityAssay[1]CellLine:MV4-11,LnCap,HT-29,A375,SKOV-3Concentration:CellsweremaintainedinRPMI1640orDMEMmediumsupplementedwith10%FBS(v/v)in5%CO2,exceptforMV4-11cells,whichwereculturedinIMDMmedium.IncubationTime:72hResult:Showedbroad-spectrumantiproliferativeactivitieswithIC50valuesof0.13,0.14,1.10,2.82and2.51µMagainstMV4-11,LnCap,SKOV-3,A375andHT29cells,respectively.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellCycleAnalysis[1]CellLine:MV4-11Concentration:0.1,0.3,1,3,9µMIncubationTime:24hResult:InducedobviousG2/Marrestinaconcentration-dependentmannerApoptosisAnalysis[1]CellLine:MV4-11Concentration:0.1,0.3,1,3,9µMIncubationTime:48hResult:SignificantlyincreasedthenumberofAnnexinV/PI-positiveMV4-11cellsinaconcentration-dependentmanner.RT-PCR[1]CellLine:MV4-11Concentration:0.1,0.3,1,3,9µMIncubationTime:24hResult:Reducedthetranscriptionofc-MYCandMYCNaswellasBCL-2,inaconcentration-dependentmanner.WesternBlotAnalysis[1]CellLine:MV4-11Concentration:0.1,0.3,1,3,9µMIncubationTime:48hResult:Decreasedtheexpressionofc-MycandBcl-2inaconcentrationdependent-mannerandupregulatedcleavedcaspase-3andcleavedPARP.体内研究PLK1/BRD4-IN-1(9b)(60mg/kg/d;IG;18days)resultsinasignificantdecreaseinaveragetumorsize,withnoobvioustoxicity[1].AnimalModel:FiveweeksoldmaleNOD-SCIDmice[1].Dosage:60mg/kg/d2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:Oralgavage,18days;tumorxenograftmodelswereestablishedbysubcutaneouslyinjecting100µLof1×108cell/mLMV4-11cellsuspensionintoNOD-SCIDmice.Result:Resultedinasignificantdecreaseinaveragetumorsize,with66%tumorgrowthinhibition,anddidn’tobviouslyaffectthebodyweightofmice.REFERENCES[1].Ning-YuWang,etal.Design,synthesis,andbiologicalevaluationof4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridinederivativesasnoveldual-PLK1/BRD4inhibitors.EurJMedChem.2020Apr1;191:112152.McePdfHeightCaution:Producthasnotbeenfullyvalidatedf