Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEARantagonist4Cat.No.:HY-151266分?式:C??H??N?O分?量:456.62作?靶點(diǎn):AndrogenReceptor作?通路:Others儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ARantagonist4(Compound67-b)?種具有?服活性的雄激素受體(AR)拮抗劑，對野?型AR的IC50為246.6nM，也AR的降解劑，DC50為2.84μM。IC50&TargetIC50:208.8nM(AR(T877A)),246.6nM(wt-AR),268.2nM(AR(F876L)),490.2nM(AR(W741L))[1]DC50:2.84μM(AR)[1]體外研究ARantagonist4(Compound67-b)(0-10μM;6days)inhibitsLNCaPand22RV1cellsproliferation[1].ARantagonist4inhibitsCYP17A1withanIC50of2.59μM[1].ARantagonist4showsantagonisticactivitieswithIC50sof490.2,208.8and268.2nMagainstAR(W741L),AR(T877A)andAR(F876L),respectively[1].CellProliferationAssay[1]CellLine:LNCaPand22RV1cellsConcentration:0-10μMIncubationTime:6daysResult:ShowedantiproliferativeactivitywithIC50sof246.6nMand590nMagainstLNCaPand22RV1cells,respectively.WesternBlotAnalysis[1]CellLine:LNCaPand22RV1cells1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0,1,5,10and20μMIncubationTime:0,2,4,8,16and24hResult:Degradedandrogenreceptorinadose-andtime-dependentmanner.體內(nèi)研究ARantagonist4(Compound67-b)(20mg/kg;p.o.;dailyfor10days)inhibitsthegrowthofandrogen-sensitiveorgans(ASOs)underthestimulationoftestosteronepropionate(TP)inrats[1].ARantagonist4(30mg/kg;p.o.;dailyfor4weeks)showsantitumoractivityinanEnzalutamide(HY-70002)-resistantc4-2b?ENZxenograftmodelinmice[1].AnimalModel:CastratedmaleSprague?Dawleyrats[1]Dosage:20mg/kgAdministration:Oraladministration,dailyfor10daysResult:Resultedinstatisticallysignificantweightreductionsinseminalvesicles(62%,p<0.01)andventralprostate(66%,p<0.01)versusthetestosteronepropionatecontrol.AnimalModel:SPFgrademaleBabl/cnudemalemice,enzalutamide-resistantc4-2b?ENZxenograftmodel[1]Dosage:30mg/kgAdministration:Oraladministration,dailyfor4weeksResult:ExhibitedaremarkabletumorregressionwithΔT/ΔC%=?14%after4weeksoftreatment.AnimalModel:MaleSprague?Dawleyrats[1]Dosage:10mg/kgAdministration:Oraladministration(PharmacokineticAnalysis)Result:PKParametersforARantagonist4(Compound67-b)inMaleSDRatsa[1]CompoundT1/2(h)Tmax(h)Cmax(ng/mL)AUC0-t(ng?h/mL)ARantagonist42.802CompoundswerePO-dosedat10mg/kginasolutionof5%DMSO+30%PEG400+65%water(0.5%MC)inmaleSDrats.Abbreviations:Cmax,maximumdrugconcentration;AUC0-t,areaunderthecurvebetween0andth;T1/2,terminalhalf-life;Tmax,thetimetakentoreachCmax.Valuesareexpressedasthemean,n=3.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].WangA,etal.Design,Synthesis,andBiologicalEvaluationofAndrogenReceptorDegradingandAntagonizingBifunctionalSteroidalAnalogsfortheTreatmentofAdvancedProstateCancer.JMedChem.2022Sep7.McePdfHeightCaution:Producthasnotbeenfullyvalidat