AZD9496-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZD9496Cat.No.:HY-12870CASNo.:1639042-08-2分⼦式:C₂₅H₂₅F₃N₂O₂分⼦量:442.47作⽤靶点:EstrogenReceptor/ERR作⽤通路:Others储存⽅式:4°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性数据体外实验DMSO:≥104.5mg/mL(236.17mM)H2O:<0.1mg/mL(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2600mL11.3002mL22.6004mL5mM0.4520mL2.2600mL4.5201mL10mM0.2260mL1.1300mL2.2600mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(protectfromlight,storedundernitrogen)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.65mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.65mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性AZD9496有效,选择性的雌激素受体(ERα)拮抗剂，IC50为0.28nM。AZD9496⼀种⼝服有效的选择性雌激素受体降解剂(SERD)IC50&TargetIC50:0.28nM(ERαantagonism),0.14nM(ERαdownregulation),0.82nM(ERαbinding)[1]体外研究ThepotencyofAZD9496withIC50of0.82nM,0.14nM,and0.28nMinERαbinding,downregulation,andantagonism,respectively.AZD9496significantlyinhibitsMCF-7cellgrowthwithEC50of0.04nM[1].SelectivityofAZD9496overothertestednuclearhormonereceptorsishigh:androgenreceptor(AR),IC50=30μM;glucocorticoidreceptor(GR),IC50=9.2μM;progesteronereceptor(PR),IC50=0.54μM[2].体内研究Significanttumorgrowthinhibitionisobservedaslowas0.5mg/kgdoseintheestrogen-dependentMCF-7xenograftmodel,wherethiseffectisaccompaniedbyadose-dependentdecreaseinPRproteinlevels,demonstratingpotentantagonistactivity.CombiningAZD9496withPI3KpathwayandCDK4/6inhibitorsleadtofurthergrowth-inhibitoryeffectscomparedwithmonotherapyalone.AZD9496,givenoncedailyorallyat5and25mg/kgproducedstatisticallysignificantincreasesinuterineweightcomparedwiththeICI182780control(P[1].AZD9496isalsotestedinalong-termestrogendeprivedmodel(LTED),usingtheHCC-1428LTEDcelllinethatgrowsintheabsenceofestrogenandisthoughttobestrepresentamodelofaromataseinhibition.AZD9496showssignificantactivity,withadoseof5mg/kggivingtumorregressionsinthismodel[2].PROTOCOLCellAssay[1]EffectofAZD9496,ICI182780,andICI47699onERαpeptideturnoverinMCF-7cells.Cellsaregrowninsteroid-freeconditionsinSILACmediacontaining13C615N4L-argininetolabelERαpeptideas“heavy”(blueline)andthenswitchedtogrowinmediacontainingunlabeledL-argininetolabelnewlysynthesizedproteinas“normal”(redline)with0.1%DMSO,300nMTamoxife,100nMAZD9496,or100nMICI182780forthetimeindicated.Datashownisrepresentativeoftwoindependentexperiments[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]InvivoefficacyofAZD9496inMCF-7xenograftmodel.MCF-7xenografts,growninmaleSCIDmice,aredoseddailywitheitherPEG/captisol(vehicle)orAZD9496(0.02,0.1,0.5,10,and50mg/kg,p.o.,q.d.).Tumorgrowthismeasuredbycaliperatregularintervalsandmeantumorvolumesplottedforeachdosedgroup.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•CancerRes.2017Oct15;77(20):5602-5613.•Oncogene.2018Aug;37(33):4581-4598.•CellProlif.2019Jul;52(4):e12612.•CellCommunSignal.2019Aug14;17(1):94.•NPJBreastCancer.2022Mar10;8(1):31.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WeirHM,etal.AZD9496:AnOralEstrogenReceptorInhibitorThatBlockstheGrowthofER-PositiveandESR1-MutantBreastTumorsinPreclinicalModels.CancerRes.2016Jun1;76(11):3307-18.[2].DeSaviC,etal.OptimizationofaNovelBindingMotifto(E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylicAcid(AZD9496),aPotentandOrallyBioavailable