Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemETelapristoneacetateCat.No.:HY-16483CASNo.:198414-31-2Synonyms:CDB-4124分子式:C??H??NO?分子量:505.65作用靶點(diǎn):ProgesteroneReceptor;Apoptosis;PARP;CDK作用通路:VitaminDRelated/NuclearReceptor;Apoptosis;CellCycle/DNADamage;Epigenetics儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Telapristoneacetate(CDB-4124)是一種強(qiáng)效的孕激素受體(PR)調(diào)節(jié)劑。Telapristoneacetate通過誘導(dǎo)細(xì)胞周期阻滯和凋亡(apoptosis)來抑制卵巢癌細(xì)胞的增殖。Telapristoneacetate能有效抑制大鼠自發(fā)性和化學(xué)誘導(dǎo)性乳腺腫瘤的發(fā)生和發(fā)展。Telapristoneacetate可用于乳腺癌和卵巢癌的研究[1][2]。IC50&TargetIC50：35.5±3.9,21.3±1.8,43.6±5.1,47.4±3.9μMofIGROV-1,IGROV-1PTES,SKOV-3,SKOV-3PTEScells,respectively[1].體外研究Telapristoneacetate(0-60μM,96h)inhibitsthegrowthofovariancancercellsresistanttoCisplatin(CDDP)(HY-17394)andPaclitaxel(PTX)(HY-B0015),withIC50valuesof35.5μM(IGROV-1),21.3μM(IGROV-1PTES),43.6μM(SKOV-3)and47.4μM(SKOV-3PTES)[1].Telapristoneacetate(30μM,48h)inducescellcyclearrestandapoptosisinIGROV-1andIGROV-1PTEScells,asevidencedbytheupregulationofp21Cip1/p27Kip1andPARPcleavage,respectively[1].Telapristoneacetate(0-10μmol/L,3-6days)inducesG1/ScellcyclearrestandtherebyinhibitscellgrowthbydownregulatingCDK2andCDK4inhumanT47Dcells[2].WesternBlotAnalysis[2]CellLine:humanT47DcellsConcentration:1μmol/LIncubationTime:3and6days1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:FailedtoaffecttheexpressionofPRA,PRB,cyclinD1,orCDK6.DecreasedERαexpression.DecreasedCDK2andCDK4expressions.CellViabilityAssay[1]CellLine:IGROV-1,IGROV-1PTES,SKOV-3,andSKOV-3PTESConcentration:0,7.5,15,30and60μMIncubationTime:96hResult:ReducedtheviabilityofIGROV-1,IGROV-1PTES,SKOV-3,andSKOV-3PTEScellsinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:IGROV-1andIGROV-1PTESConcentration:30μMIncubationTime:48hResult:Causedanincreaseintheabundanceofthecellcycleinhibitorp27kip1inbothparentalandPTEScells.Increasedcyclindependentkinaseinhibitorp21cip1,cellcyclearrestassociatedprotein.ShowednosignificantdifferencesintheexpressionofG1regulatoryproteinsCDk2andcyclinEbetweenparentalandPTEScells.InducedthecleavageofPARP,indicatingitinducescellapopotosis.CellProliferationAssay[2]CellLine:humanT47DcellsConcentration:0,0.1,1.0and10μmol/LIncubationTime:3and6daysResult:Didnotaffectcellgrowthaftereither3daysor6daysoftreatmentat0.1μmol/L.Suppressedcellgrowthinadose-dependentmannerat1.0and10μmol/L.CellCycleAnalysis[2]CellLine:humanT47DcellsConcentration:0.1,1.0and10μmol/LIncubationTime:3and6days2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:DecreasedthepercentageofcellsinSphasefrom12.2%(control)to8.5%after3days.DecreasedthepercentageofcellsinSphasefrom14.1%(control)to9.3%after6days.SignificantincreasedtheproportionofcellsintheG1/G0phaseafter6days.InhibitedthetransitionofcellsfromG1toSphaseofthecellcycle.體內(nèi)研究Telapristoneacetate(20,70,and200mg/kg,i.g.,dailyfor24months)inhibitsspontaneousmammarycarcinogenesisbyreducinglobularhyperplasiaanddevelopmentofbenigntumorsinrats[2].Telapristoneacetate(3and30mg/pellet,s.c.,over84days,initiated6dayspost-MNU)suppressesthedevelopmentofprecancerouslesionsandcarcinogen-inducedestrogenreceptor(ER)+mammarytumorsinrats[2].AnimalModel:FemaleSDrats[2]Dosage:20,70,and200mg/kgAdministration:i.g.,dailyfor24monthsResult:Showednosignificantchangesat20and70mg/kgdoses.Slightlydecreasedthebodyweight(12.5%)at200mg/kgbutthedifferencewithcontrolgroupwasnotsignificant.Exhibitednosubstantialdifferencesintumorsorotherpathologiesininternalorgans(liver,spleen,heart,lung,intestine,brain,kidneys),comparedtocontrol.Decreasedfibroadenomasandhyperplasticlesionswithatypia.Increasecysticformationsandinducedcalcificationsamongmammaryglandparenchyma.Reducedductallateralbranchingthatleadstoreductioninlobularstructuresinmammarygland.AnimalModel:FemaleSDrats(50daysold)intraperitoneallyinjectedwithN-methyl-N-nitrosourea(MNU)[2]Dosage:3.0and30.0mg/pelletAdministration:s.c.,over84days,initiated6dayspost-MNUResult:SignificantlydecreasedthepercentageofKi-67-positivecellsfrom16.5%(control)to9.1%.Suppressedcellproliferationandinducesapoptosis.Showedaveragetumorlatencyof74daysforthelow-doseand87daysforthehigh-dose.Suppressedtheincidenceandmultiplicityofmammarytumorsinadose-dependentmanner.Decreasedtumorincidencefrom85%(control)to60%(lowdose)and35%(highdose).3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEDecreasedtumormultiplicity,from3.0tumors/ratinthecontrolgroupto2.2and1.1tumors/ratinthelow-andhigh-dose,respectively.Resultedinanincreaseinintercellularspacesbetweentumorcellsandthedevelopmentofcysticformations.Decreasedserumprogesterone,buthadnoeffectonestradiol.SuppressedPRexpressioninmammarytumors.Showednosignificantchangesinanimalbodyweight.REFERENCESWiehleR,etal.CDB-4124,aprogesteronereceptormodulator,inhibitsmammarycarcinogenesisbysuppressingcellproliferationandinducingapoptosis.CancerPrevRes(Phila).2011Mar;4(3):414-24.CarlosDGamarra-Luques,etal.Resistancetocisplatinandpaclitaxeldoesnotaffectthesensitivityofhumanovariancancer