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- •SciRep.2017Jul26;7(1):6501.
- •BiochemBiophysResCommun.2017Nov23.pii:S0006-291X(17)32327-6.
- •EvidBasedComplementAlternatMed.2016;2016:5850739.
| Description | Mifepristoneisaprogesteronereceptor(PR)antagonist(IC50=0.2nM)inaT47Dcell-basedassay,alsoisaglucocorticoidreceptor(GR)antagonist(IC50=2.6nM)inanA549cell-basedassay. |
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| IC50&Target | IC50:0.2nM(progesteronereceptor,inT47Dcells),2.6nM(glucocorticoidreceptor,inA549cells)[1] |
| InVitro | Thediscoveryofthefirstcompetitiveprogesteroneantagonist,Mifepristone,hasstimulatedanintensesearchformorepotentandmoreselectiveantiprogestins[1].Cellgrowthisevaluatedafter4daysofexposuretoMifepristoneat10μM,aconcentrationclosetotheplasmaconcentrationachievableinhumans.TheantiproliferativeeffectofCisplatinispotentiatedwhenadministeredincombinationwithMifepristoneinHeLacells.TheIC50ofCisplatinincombinationwithMifepristoneislower(14.2μM)thanthatofCisplatinalone(34.2μM)inHeLacellswithanapproximately2.5-folddifference.AftertreatmentwithMifepristone,theaccumulationofintracellularCisplatininHeLacellsis2-foldgreater,representingasignificantdifference(p=0.009),comparewithCisplatinalonefrom0.79to1.52μg/mgofprotein[2]. |
| InVivo | ThecervixtumorxenograftmodelsaretreatedwithCisplatinalone,thereisatumorgrowthinhibitioncomparewithcontrolgroup.However,thetumorweightlossisevenmoresignificant(p<0.05) with="" the="" combination="" of="" cisplatin="" and="" mifepristone="" at="" the="" doses="" used,="" showing="" a="" decrease="" of="" ~50%="" compared="" with="" the="" treatments="" alone="" by="" the="" end="" of="" the="">[2].AdultmaleSprague-Dawleyratsaresubjectedtoa4-daybinge-likeEtOHadministrationregimen(3to5g/kg/i.g.every8hoursdesignedtoproducepeakbloodEtOHlevels(BELs)of<300 mg/dl).="" subgroups="" of="" animals="" receive="" s.c.="" injection="" of="" mifepristone="" (20="" or="" 40="" mg/kg="" in="" peanut="" oil).="" although="" mifepristone="" produces="" no="" significant="" changes="" in="" behavior="" of="" etoh-naïve="" animals,="" pretreatment="" with="" mifepristone="" (40="" mg/kg)="" significantly="" reducesthe="" severity="" of="" etoh="" withdrawal.="" asignificant="" interaction="" between="" diet="" and="" drug,="" f(5,55)="3.92,"><0.05, such="" that="" etoh-treated="" animals="" receiving="" vehicle="" or="" 20="" mg/kg="" of="" mifepristone="" displayssignificantly="" more="" signs="" of="" etoh="" withdrawal="" than="" does="" etoh-naïve="" animals="" receiving="" the="" same="" drug="" treatment.="" importantly,="" treatment="" with="" 40="" mg/kg="" of="" mifepristone="" significantly="" reduces="" the="" severity="" of="" etoh="" withdrawal,="" in="" a="" dose-dependent="">[3]. |
| ClinicalTrial | ViewMoreCollapse |
| References |
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Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent. | ||||||||||||||||
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| KinaseAssay [1] | T47Dhumanbreastcancercellsareplatedin96-welltissuecultureplatesat10,000cellsperwellinassaymedium[RPMImediumwithoutphenolredcontaining5%(v/v)charcoal-treatedFBSand1%(v/v)penicillin-streptomycin].Twodayslater,themediumisdecantedandMifepristoneorcontrolisaddedatafinalconcentrationof0.1%(v/v)dimethylsulfoxideinfreshassaymedium.Twenty-fourhourslater,analkalinephosphataseassayisperformedusingaSEAPkit.Briefly,themediumisdecantedandthecellsarefixedfor30minatroomtemperaturewith5%(v/v)formalin.ThecellsarewashedonceatroomtemperaturewithHanks’bufferedsalinesolution.Equalvolumes(0.05mL)of1×dilutionbuffer,assaybuffer,and1:20substrate/enhancermixturearethenadded.Aftera1-hincubationatroomtemperatureinthedark,thelysateistransferredtoawhite96-wellplateandluminescenceisreadusingaLuminoSkanAscent[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. | ||||||||||||||||
| CellAssay [2] | Mifepristoneisreconstitutedinabsoluteethanolandstored(-20˚C),andthendilutedwithappropriatemediabeforeuse[2]. TheHeLaandCaSkihumancervicalcancercelllinesareused.TheeffectofMifepristoneonproliferationofcellsexposedtoCisplatinisevaluatedusingtheXTTassay.TheassayisbasedonthecleavageoftheyellowtetrazoliumsaltXTTtoformanorangeformazandyebymetabolicallyactivecells.Theprocedureisasfollows.Cellsareseededinto96-wellplates;Costaratadensityof6×103viablecellsperwellin100μLculturemedium.AttheendoftreatmentwithCisplatinaloneorthecombinationofCisplatinplusMifepristone,50μLXTTisaddedtoeachwell(finalconcentration0.3mg/mL),followbyincubationfor4hinahumidifiedatmospherecontaining5%CO2at37˚C.Theabsorbanceofthesamplesismeasuredspectrophotometricallyat492nmusingamicrotiterplateELISAreader[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. | ||||||||||||||||
| AnimalAdministration [2][3] | MifepristoneissUSPendedinpeanutoil(Rat)[3]. Mice[2] | ||||||||||||||||
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| MolecularWeight | 429.59 | ||||||||||||
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| Formula | C₂₉H₃₅NO₂ | ||||||||||||
| CASNo. | 84371-65-3 | ||||||||||||
| Storage |
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| Shipping | RoomtemperatureincontinentalUS;mayvaryelsewhere | ||||||||||||
| Solvent&Solubility | DMSO:≥59mg/mL *"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation=""> Purity:98.17% |
