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Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMifepristoneCat.No.:HY-13683CASNo.:84371-65-3Synonyms:RU486;RU38486分⼦式:C₂₉H₃₅NO₂分⼦量:429.59作⽤靶点:ProgesteroneReceptor;GlucocorticoidReceptor;NOSynthase;Autophagy作⽤通路:Others;Immunology/Inflammation;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(232.78mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3278mL11.6390mL23.2780mL5mM0.4656mL2.3278mL4.6556mL10mM0.2328mL1.1639mL2.3278mL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。-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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂:0.5%CMC-Na/salinewaterSolubility:10mg/mL(23.28mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂:10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.82mM);Clearsolution3.请依序添加每种溶剂:10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.82mM);Clearsolution4.请依序添加每种溶剂:10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.82mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Mifepristone(RU486)体酮受体(PR)和糖⽪质激素受体(GR)拮抗剂,体外实验中的IC50值分别为0.2nM和2.6nM[1]。IC50&TargetIC50:0.2nM(progesteronereceptor,inT47Dcells),2.6nM(glucocorticoidreceptor,inA549cells)[1]体外研究Thediscoveryofthefirstcompetitiveprogesteroneantagonist,Mifepristone,hasstimulatedanintensesearchformorepotentandmoreselectiveantiprogestins[1].Cellgrowthisevaluatedafter4daysofexposuretoMifepristoneat10μM,aconcentrationclosetotheplasmaconcentrationachievableinhumans.TheantiproliferativeeffectofNSC119875ispotentiatedwhenadministeredincombinationwithMifepristoneinHeLacells.TheIC50ofNSC119875incombinationwithMifepristoneislower(14.2μM)thanthatofNSC119875alone(34.2μM)inHeLacellswithanapproximately2.5-folddifference.AftertreatmentwithMifepristone,theaccumulationofintracellularNSC119875inHeLacellsis2-foldgreater,representingasignificantdifference(p=0.009),comparewithNSC119875alonefrom0.79to1.52μg/mgofprotein[2].体内研究ThecervixtumorxenograftmodelsaretreatedwithNSC119875alone,thereisatumorgrowthinhibitioncomparewithcontrolgroup.However,thetumorweightlossisevenmoresignificant(p[2].AdultmaleSprague-Dawleyratsaresubjectedtoa4-daybinge-likeEtOHadministrationregimen(3to5g/kg/i.g.every8hoursdesignedtoproducepeakbloodEtOHlevels(BELs)of[3].PROTOCOLCellAssay[2]TheHeLaandCaSkihumancervicalcancercelllinesareused.TheeffectofMifepristoneonproliferationofcellsexposedtoNSC119875isevaluatedusingtheXTTassay.TheassayisbasedonthecleavageoftheyellowtetrazoliumsaltXTTtoformanorangeformazandyebymetabolicallyactivecells.Theprocedureisasfollows.Cellsareseededinto96-wellplates;Costaratadensityof6×103viablecellsperwellin100μLculturemedium.AttheendoftreatmentwithNSC119875aloneorthecombinationofNSC119875plusMifepristone,50μLXTTisaddedtoeachwell(finalconcentration0.3mg/mL),followbyincubationfor4hinahumidifiedatmospherecontaining5%CO2at37˚C.Theabsorbanceofthesamplesismeasuredspectrophotometricallyat492nmusingamicrotiterplateELISAreader[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalMice[2]Administration[2][3]FemaleNudemicebetween6-8weeksofageareimplantedsubcutaneouslywith6×106HeLacellsinaflank.Oncetumorsare~5×5mm,theanimalsarepair-matchedintotreatmentandcontrolgroups.Eachgroupconsistof8tumor-bearingmice.Theintraperitonealadministrationofdrugsorvehiclebeginonday0.NSC119875,asasingleagent,isadministeredintraperitoneallyatadoseof3mg/kgdailyondays1through3;thedoseofMifepristone,asasingleagent,is2mg/kg/daysubcutaneouslyfor3days;inthecombinationstudy,themiceconcurrentlyreceiveNSC119875onthesameschedule,andMifepristoneatthesamedose3daysprevioustotheadministrationofNSC119875.Thecontrolanimalsreceiveonlythevehicle.Afteradministrationofthedrugs,miceareweighedandthetumorsaremeasuredwithacalipertwiceweekly.Thetumorweightiscalculated.Experimentisconductedfor74days,afterwhichtimeallanimalsareweighedandhumanelyeuthanized.Rats[3]AdultmaleSprague-Dawleyrats,weighingbetween224and245guponarrival,areused.Mifepristone(20or40mg/kg)orvehicle(peanutoil)areadministeredsubcutaneously(s.c.)oncedailyfollowingthe0800administrationofEtOHorcontroldiet.Mifepristoneissuspendedinpeanutoilandsonicatedfor30minutesatleast24hourspriortoinjection,itisthenstoredat4°Cuntilneeded.Suspensionisvortexedfor10to15minutespriortoandasneededthroughoutdosing.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2020May6;12(542):eaba0769.•BrJPharmacol.2021Aug;178(15):2976-2997.•Oncogene.2021Sep;40(35):5367-5378.•IntJCancer.2021Dec22.•OxidMedCellLongev.2021Jun23;2021:9981480.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JiangW,etal.Newprogesteronereceptorantagonists:phosphorus-containing11beta-aryl-substitutedsteroids.BioorgMedChem.2006Oct1;14(19):6726-32.[2].JuradoR,etal.NSC119875cytotoxicityisincreasedbymifepr
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