Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEARantagonist17Cat.No.:HY-178148CASNo.:3064715-04-1分子式:C??H??F?N?O?S?分子量:499.53作用靶點(diǎn):AndrogenReceptor作用通路:VitaminDRelated/NuclearReceptor儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性ARantagonist17是一種具有選擇性、口服活性、不易透過血腦屏障的雄激素受體(AR)拮抗劑(IC50=0.010μM)，可有效阻斷AR二聚化和核轉(zhuǎn)位，并在多種去勢(shì)抵抗性前列腺癌(CRPC)細(xì)胞中表現(xiàn)出強(qiáng)效作用。ARantagonist17對(duì)多種耐藥性AR突變體表現(xiàn)出優(yōu)異的療效。ARantagonist17在LNCaP異種移植模型中抑制腫瘤生長(zhǎng)，且無明顯毒性。ARantagonist17可用于去勢(shì)抵抗性前列腺癌(CRPC)的研究[1]。體外研究ARantagonist17(CompoundC13)showsexcellentARantagonisticactivityandantiproliferativeeffectsagainstAR-positivePCacelllines(LNCaP(IC50=1.02μM),C4?2B(IC50=3.86μM),22RV1(IC50=8.45μM),andVCaP(IC50=5.72μM)),accompaniedbylowtoxicityonnormalcelllines3T3andGes-1(IC50>20μM)[1].ARantagonist17(0.2-2μM,2weeks)completelyinhibitsclonalproliferationinLNCaPcells[1].ARantagonist17(0.02-2μM,48h)dose-dependentlysuppressesthedihydrotestosterone(DHT)-inducedtranscriptionallevelsofprostate-specificantigen(PSA),andremarkablysuppressesmRNAlevelsoftwoAR-regulateddownstreamgenes,FKBP5andTMPRSS2inLNCaPcells[1].ARantagonist17(0.1-10μM,24h)dose-dependentlyinhibitsendogenousPSAproteinexpressionbuthasnosignificanteffectonARproteinexpressioninLNCaPcells[1].ARantagonist17(0.1-10μM,4h)inhibitsDHT-inducedARdimerizationinadose-dependentmanner,andcompletelyblocksthisprocessat10μMin293Tcells[1].ARantagonist17(10μM,8h)cancauseARtoremainmainlyinthecytoplasmandeffectivelypreventARnucleartranslocationinLNCaPcells[1].ARantagonist17demonstratesexcellentantagonisticactivityagainsttheseclinicallyprevalentARresistancemutations,ARF877L/T878A(IC50=0.35μM),ARW742C(IC50=0.50μM),ARF877L(IC50=0.070μM)[1].ARantagonist17(2μM,48h)significantlysuppresseseightclinicallyrelevantPCarecurrencemarkers:1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEKLK3(encodingPSA),TMPRSS2,KLK2,NKX3.1,SLC45A3,PMEPA1,TARP,andTM4SF1,alongsidecancer-relatedprocesses,apoptosisregulatorsSTK39,HERC3,andGRIN3AinLNCaPcells[1].ARantagonist17(2μM,48h)significantlyinhibitstheexpressionofthepan-cancer-relatedbiomarkersforDNAbiosynthesisandrepair,includingEXO1,CYP11A1,PGC,RRM2,andFAM111BinLNCaPcells[1].CellProliferationAssay[1]CellLine:LNCaPcellsConcentration:0.2μM,2μMIncubationTime:2weekResult:Inhibitedclonalproliferationataconcentrationof2.0μM,showingbetterinhibitoryactivityagainstclonalproliferationthanEnz0.2μM.WesternBlotAnalysis[1]CellLine:LNCaPcellsConcentration:0.1Μm,1μM,10μMIncubationTime:24hResult:InhibitedendogenousPSAproteinexpressionbuthadnosignificanteffectonARproteinexpressioninLNCaPcells.RT-PCR[1]CellLine:LNCaPcellsConcentration:0.02μM,0.2μM,2μMIncubationTime:48hResult:SuppressedtheDHT-inducedtranscriptionallevelsofprostate-specificantigen(PSA),andremarkablysuppressedmRNAlevelsoftwoAR-regulateddownstreamgenes,FKBP5andTMPRSS2.WesternBlotAnalysis[1]CellLine:LNCaPcellsConcentration:10μMIncubationTime:8hResult:EffectivelyinhibitedDHT-inducedARnucleartranslocation;ARmainlyremainsinthecytoplasm.RT-PCR[1]2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:LNCaPcellsConcentration:2μMIncubationTime:48hResult:SignificantlysuppressedeightclinicallyrelevantPCarecurrencemarkers:KLK3(encodingPSA),TMPRSS2,KLK2,NKX3.1,SLC45A3,PMEPA1,TARP,andTM4SF1,alongsidecancer-relatedprocesses,apoptosisregulatorsSTK39,HERC3,andGRIN3AinLNCaPcells.Significantlyinhibitedtheexpressionofthepan-cancer-relatedbiomarkersforDNAbiosynthesisandrepair,includingEXO1,CYP11A1,PGC,RRM2,andFAM111BinLNCaPcells.體內(nèi)研究ARantagonist17(5mg/kg,oralgavage,2-8h)haslowblood-brainbarrierpermeabilityinSDRats,mayhavebettersafetyandreducecentralnervoussystem-relatedsideeffects[1].ARantagonist17(40mg/kg,oralgavage,twicedailyfor32days)demonstratessignificanttumorgrowthsuppressionthroughoutthetreatmentdurationanddoesnotinducesignificantbodyweightlossorothersignsoftoxicityduringtheexperimentinCB17SCIDmice[1].AnimalModel:SDRats[1]Dosage:5.0mg/kgAdministration:OralgavageResult:Hadlowblood-brainbarrierpermeabilityinSDRats.AnimalModel:LNCaPcells(1×107)wereimplantedsubcutaneouslyintotherightflanksofthe6-week-oldmaleCB17SCIDmice[1].Dosage:40mg/kgAdministration:Oralgavage,twicedailyfor32daysResult:Thetumorgrowthinhibition(TGI)ofARantagonist17was123.41%.Exhibitedgoodtoleranceanddidnotinducesignificantbodyweightlossorothersignsoftoxicityduringtheexperiment.REFERENCESLiaoJ,etal.DiscoveryofN-(thiazol-2-yl)FuranamideDerivativesasPotentOrallyEfficaciousARAntagonistswithLowBBBPermeability.JMedChem.2025Sep25;68(18):19688-19713.McePdfHe