SC912-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESC912Cat.No.:HY-161409分子式: C??H??Cl?F?N?O?分子量: 493.27作用靶點(diǎn): AndrogenReceptor;Apoptosis作用通路: VitaminDRelated/NuclearReceptor;Apoptosis儲(chǔ)存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性SC912是一種AR-V7(IC50=0.36μM)抑制劑，擁有安全性，高效性和選擇性，直接和AR-FL和AR-V7蛋白結(jié)合，通過(guò)抑制增殖，誘導(dǎo)細(xì)胞周期停止和凋亡來(lái)發(fā)揮抗癌活性[1]。體外研究SC912(0.1-10μM;24h)effectivelyinhibitsARactivationinPC3Cells.NoinhibitionofGRandPR(ARIC50=0.57μM)[1].SC912(0.03-100μM;1h)bindingtoAR-FLandAR-V7isattenuatedin293TcellsdeletedforAR-NTDaminoacids507-531.Aminoacids507-531areessentialfortheantagonisticactivity[1].SC912(2μM;24h)stronglyrepressesthetranscriptionofAR-regulatedgenes(PSA,FKBP5,TMPRSS2)thatareuniquelyregulatedbyAR-V7intheLNCaP95cellmodel,suggestingeffectiverepressionofAR-V7-mediatedtranscriptionalactivity[1].SC912(1μM;24h)leadstoG1phaseblockadeandcausesapoptosisinLNCaP,VCaPand22Rv1cells[1].SC912(3μM;5h)significantlyreducestheintranuclearaccumulationofAR-FLandAR-V7inLNCaPandLNCaP-AR-V7cells,suggestingthatisabletoeffectivelyblockthenuclearlocalizationofAR-V7.SC912alsosignificantlyreducsthebindingofARproteinstothechromatin[1].ApoptosisAnalysis[1]CellLine:LNCaP,VCaP,22Rv1cell,PC3Concentration:1μMIncubationTime:24hResult:SC912ledtosignificantPARPcleavageinLNCaP,VCaP,and22Rv1cells,indicatingeffectiveinductionofapoptosis.Flowcytometryanalysisshowedanincreaseinthe1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEpercentageofapoptoticcellsinLNCaP,VCaP,and22Rv1celllineswithSC912.ThisfurthersupportedthefindingthatSC912inducesapoptosiseffectivelyinAR-positivecells.RealTimeqPCR[1]CellLine:LNCaP,VCaP,22Rv1Concentration:0,0.1,0.3,1,3μMIncubationTime:24hResult:SC912-dependentdose(0.33μM)impairedthetranscriptionofAR-regulatedgenes(PSA,FKBP5andTMPRSS2)intheseprostatecancercelllines.ThisindicateseffectiveinhibitionofARsignalingbySC912.Theinhibitionofgeneexpressionwasdose-dependent.CellCycleAnalysis[1]CellLine:LNCaP,VCaP,22Rv1cell,PC3Concentration:3μMIncubationTime:48hResult:InducedasignificantG1/Sphasearrestinthetreatedcells.Thiseffectwasdose-dependent,withhigherconcentrationsofSC912leadingtoamorepronouncedaccumulationofcellsintheG1phase,suggestingablockadeinthetransitionfromG1toSphase.體內(nèi)研究SC912(60mg/kg;i.p.;5timesdaysfor3weeks)haltsthegrowthofVCaPtumorseffectively.Nonoticeablelossinbodyweightofthemice,indicatinggoodtolerabilityattheadministereddose[1].SC912(90mg/kg;i.p.;5daysaweekfor3weeks)alleviatestumorprogressioneveninthishighlycastration-resistant22Rv1model[1].AnimalModel:NOD-SCIDmiceimplantedwithVCaPcells[1]Dosage:60mg/kg,fivetimesaweekfor3weeksAdministration:i.p.Result:SC912wasfoundtoeffectivelyrepresstumorgrowthinthexenograftmodels.ThiswasevidencedbyamarkedreductionintumorsizeinmicetreatedwithSC912comparedtothosetreatedwithvehiclecontrols.TheserumlevelsofhumanPSA,amarkerofARactivity,wereconsiderablylower,indicatingeffectiveinhibitionofARsignaling.2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAnimalModel:miceimplantedwith22Rv1cells[1]Dosage:90mg/kg,fivetimesaweekfor3weeksAdministration:i.p.Result:SC912markedlymitigatedtumorprogressioninthishighlycastration-resistant22Rv1model.ThegrowthrateoftumorswassignificantlyreducedintheSC912-treatedgroupcomparedtothevehicle-treatedcontrols.ReductionintumorsizewasassociatedwithasignificantdecreaseinAR-drivengeneexpressionwithinthetumors,highlightingSC912’scapabilitytointerruptAR-V7-mediatedsignalingpathwaysevenunderhighAR-V7expressingconditions.REFERENCESQianhuiYetal.SC912inhibitsAR-V7activityincastration-resistantprostatecancerbytargetingtheandrogenreceptorN-terminaldomainOncogene.2024MarM