SC428-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESC428Cat.No.:HY-164373CASNo.:1898232-70-6分?式:C??H??F?N?OS分?量:337.32作?靶點:AndrogenReceptor;Apoptosis作?通路:VitaminDRelated/NuclearReceptor;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY?物活性SC428雄性激素受體(AR)的抑制劑，靶向ARN-端結構域。SC428有效地降低了AR-V7、ARv567es以及全長AR(AR-FL)及其LBD突變體的轉激活。SC428顯著抑制雄激素刺激的AR-FL核易位、染?質結合和AR調節(jié)的因轉錄。SC428在體外抑制腫瘤細胞的增殖。SC428在移植22Rv1的??體內通過誘導凋亡抑制腫瘤細胞?長[1]。體外研究SC428(10nM-1μM,48h),whichinhibitsAR-V7(IC50is0.42μM)andARv567es(IC50is1.31μM)activityin293T(PSA-Luc)[1].SC428(5μM,5h)reversesDHT-inducedthermalstabilizationofAR-FL(EC50is0.31μM)inLNCaP(CETSA),inhibitsligand-inducedactivationofARinaconcentration-dependentmannerandisanantagonistoftheF887Lmutant[1].SC428(1,2.5and5μM,30min)inhibitstheproliferationofLNCaP(IC50is1.39μM),VCaP(IC50is1.01μM),22RV1(IC50is1.13μM)AR-positivecellline.Theabilityofanti-proliferationisweakinAR-negativecelllinePC3(IC50is6.49μM)[1].SC428(5μM,5h)attenuatestranscriptionofAR-regulatedgenesinLNCaP-ARcells(ChIPexperiments),blocksAR-FLchromatinbinding(confocalimagingexperiments),andreducesnucleartranslocation[1].SC428(2.5,5μmol/L,24h)inhibitsARsignalinginprostatecancercellsthatoverexpressAR-V7[1].SC428(0.5,1,2.5and5μM,24h)hasinhibitoryeffectsonbothLNCaP-ARV7andLNCaP-wtcells(Enzalutamide(HY-70002)-resistant),inhibitingPSAandUBE2CatbothproteinandmRNAlevels(WBandqPCR)[1].SC428(5μM,5h)disruptsAR-V7dimer(immunoprecipitationassay)andnuclearlocalization(confocal1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEimagingtechnique)in22RV1cells[1].RealTimeqPCR[1]CellLine:LNCaP-ARConcentration:5μmol/LIncubationTime:24hResult:InhibitedAR-FLtranscriptionsignificantlyandrogen-mediatedmRNAexpression.RealTimeqPCR[1]CellLine:22Rv1Concentration:2.5and5μmol/LIncubationTime:24hResult:2.5mmol/LSC428reducedAR-regulatedgenemRNAto50%ofcontrols,whereas5mmol/LSC428furtherreduceditto10%to30%ofcontrols.AR-V7-dependentArsignalingwasblockedin22Rv1cells.RealTimeqPCR[1]CellLine:LNCaP-AR-V7Concentration:0.5,1,2.5and5μmol/LIncubationTime:24hResult:InhibitedtheexpressionofPSAgeneinLNCaP-AR-V7cellsandsignificantlydecreasedthemRNAlevelofAR-V7specificgeneUBE2C.WesternBlotAnalysis[1]CellLine:LNCaP-AR-V7Concentration:0.5,1,2.5and5μmol/LIncubationTime:24hResult:InhibitedPSA-LucwithequalpotencyinLNCaP-AR-V7andLNCaP-ARWTcells.WesternBlotAnalysis[1]CellLine:LNCaP-AR-V7，22Rv1Concentration:5μmol/L2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:5hResult:ReducedAR-V7homodimer.CellProliferationAssay[1]CellLine:LNCaP,VCaP,22Rv1,PC3Concentration:1,2.5and5μmol/LIncubationTime:30minResult:InhibitedtheproliferationofthreeAR-positivecelllines,andtheanti-proliferationeffectofSC428ontheAR-negativecelllinePC3was6-foldlowerthanthatontheAR-positivecellline.CellProliferationAssay[1]CellLine:LNCaP-ARConcentration:0.1μM-10μMIncubationTime:30hResult:OvercametheENZ-resistantARsignalingandcellproliferationdrivenbyAR-V7.體內研究SC428(60mg/kg;intraperitonealinjection;oncedaily;18days)inhibitedAR-V7tumorgrowthbyinducingtumorcellapoptosisinmice[1].SC428(90mg/kg;intraperitonealinjection;fivetimesaweek;3weeks)inhibitedthegrowthofAR-V7inmice[1].AnimalModel:22Rv1cellsweresubcutaneouslyinjectedintotherightflankofmaleNu/Numice[1].Dosage:60mg/kgAdministration:Intraperitonealinjection(i.p.);dailyroute5daysaweek;3weeksResult:Reducedthetumorgrowthby50%,themicedidnotloseweight,andthetumorPSAwasreducedtoundetectablelevels.AnimalModel:22Rv1cellsweresubcutaneouslyinjectedintotherightflankofmaleNu/Numice.MaleNu/Numiceweresurgicallycastratedwhentheimplanted22Rv1cellsachievedanaveragetumorsizeof200mm3[1].Dosage:90mg/kg3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:Intraperitonealinjection(i.p.);dailyroute5daysaweek;3weeksResult:InhibitedthegrowthofprostatecancerwithhighexpressionofAR-V7.Gooddrugtolerance,nosignificantweightloss.REFERENCES[1].QianhuiYi,etal.DiscoveryofaSmall-MoleculeInhibitorTargetingtheAndrogenReceptorN-TerminalDomainforCastration-ResistantProstateCancer.20