Mifepristoneisaprogesteronereceptor(PR)antagoNIST(IC50=0.2nM)inaT47Dcell-basedassay,alsoisaglucocorticoidreceptor(GR)antagonist(IC50=2.6nM)inanA549cell-basedassay.CustomerValidation•SciRep.2017Jul26;7(1):6501.•BiochemBiophysResCommun.2017Nov23.pii:S0006-291X(17)32327-6.•EvidBasedComplementAlternatMed.2016;2016:5850739.DescriptionMifepristoneisaprogesteronereceptor(PR)antagonist(IC50=0.2nM)inaT47Dcell-basedassay,alsoisaglucocorticoidreceptor(GR)antagonist(IC50=2.6nM)inanA549cell-basedassay.IC50&TargetIC50:0.2nM(progesteronereceptor,inT47Dcells),2.6nM(glucocorticoidreceptor,inA549cells)[1]InVitroThediscoveryofthefirstcompetitiveprogesteroneantagonist,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].InVivoThecervixtumorxenograftmodelsaretreatedwithCisplatinalone,thereisatumorgrowthinhibitioncomparewithcontrolgroup.However,thetumorweightlossisevenmoresignificant(p[2].AdultmaleSprague-Dawleyratsaresubjectedtoa4-daybinge-likeEtOHadministrationregimen(3to5g/kg/i.g.every8hoursdesignedtoproducepeakbloodEtOHlevels(BELs)of[3].ClinicalTrialViewMoreCollapseReferences[1].JiangW,etal.Newprogesteronereceptorantagonists:phosphorus-containing11beta-aryl-substitutedsteroids.BioorgMedChem.2006Oct1;14(19):6726-32.[2].JuradoR,etal.Cisplatincytotoxicityisincreasedbymifepristoneincervicalcarcinoma:aninvitroandinvivostudy.OncolRep.2009Nov;22(5):1237-45.[3].Sharrett-FieldL,etal.MifepristonePretreatmentReducesEthanolWithdrawalSeverityInVivo.AlcoholClinExpRes.2013Aug;37(8):1417-23.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM2.3278mL11.6390mL23.2780mL5mM0.4656mL2.3278mL4.6556mL10mM0.2328mL1.1639mL2.3278mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.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]FemaleNudemicebetween6-8weeksofageareimplantedsubcutaneouslywith6×106HeLacellsinaflank.Oncetumorsare~5×5mm,theanimalsarepair-matchedintotreatmentandcontrolgroups.Eachgroupconsistof8tumor-bearingmice.Theintraperitonealadministrationofdrugsorvehiclebeginonday0.Cisplatin,asasingleagent,isadministeredintraperitoneallyatadoseof3mg/kgdailyondays1through3;thedoseofMifepristone,asasingleagent,is2mg/kg/daysubcutaneouslyfor3days;inthecombinationstudy,themiceconcurrentlyreceiveCisplatinonthesameschedule,andMifepristoneatthesamedose3daysprevioustotheadministrationofCisplatin.Thecontrolanimalsreceiveonlythevehicle.Afteradministrationofthedrugs,miceareweighedandthetumorsaremeasuredwithacalipertwiceweekly.Thetumorweightiscalculated.Experimentisconductedfor74days,afterwhichtimeallanimalsareweighedandhumanelyeuthanized.Rat[3]AdultmaleSprague-Dawleyrats,weighingbetween224and245guponarrival,areused.Mifepristone(20or40mg/kg)orvehicle(peanutoil)areadministeredsubcutaneously(s.c.)oncedailyfollowingthe0800administrationofEtOHorcontroldiet.Mifepristoneissuspendedinpeanutoilandsonicatedfor30minutesatleast24hourspriortoinjection,itisthenstoredat4°Cuntilneeded.Suspensionisvortexedfor10to15minutespriortoandasneededthroughoutdosing.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].JiangW,etal.Newprogesteronereceptorantagonists:phosphorus-containing11beta-aryl-substitutedsteroids.BioorgMedChem.2006Oct1;14(19):6726-32.[2].JuradoR,etal.Cisplatincytotoxicityisincreasedbymifepristoneincervicalcarcinoma:aninvitroandinvivostudy.OncolRep.2009Nov;22(5):1237-45.[3].Sharrett-FieldL,etal.MifepristonePretreatmentReducesEthanolWithdrawalSeverityInVivo.AlcoholClinExpRes.2013Aug;37(8):1417-23.MolecularWeight429.59FormulaC₂₉H₃₅NO₂CASNo.84371-65-3StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥59mg/mL*"

托烷司琼临床评价药物相关作用适应症托烷司琼CAS号:89565-68-4英文名称:Tropisetron英文同义词:icf205-930;TROPICACID;TROPISETRON;SS-TROPISETRON;BETA-TROPISETRON;Tropisetron(ICS205930);TROPISHTRONHYDROCHLORIDE;Indole-3-carbonylchloride;3-Tropanylindole-3-carboxylate;lαH，5Αh-Tropan-3α-ylindole-3-carboxylate中文名称:托烷司琼中文同义词:托普西隆;托普西龙;曲匹西龙;托烷司琼;Β-托烷司琼;CS-348;Β-内托烷司琼;吲哚-3-甲酰氯;Β-托烷司琼(光学异构体);Β-托烷司琼,托烷司琼异构体CBNumber:CB3236404分子式:C17H20N2O2分子量:284.35MOLFile:89565-68-4.mol化学性质安全信息用途供应商112化学性质安全信息用途供应商112托烷司琼化学性质熔点:201-202°C沸点:448.5±35.0°C(Predicted)密度:1.26储存条件:2-8°C溶解度:H2O:soluble形态:solid酸度系数(pKa):15.38±0.30(Predicted)颜色:whiteCAS数据库:Chemicalbook89565-68-4(CASDataBaseReference)安全信息WGKGermany:3托烷司琼化学药品说明书托烷司琼|药物应用信息托烷司琼性质、用途与生产工艺临床评价Sorbe等报道本品对含顺铂(剂量50～89mg/m2)化疗方案引起的急性呕吐完全控制率为63%。58例恶性肿瘤化疗所致恶心、呕吐者，应用托烷司琼或昂丹司琼8mg分别在同一病人前后2个化疗周期的第1d给药前30min静脉注射，并用地塞米松10mg静脉滴注。结果两药控制急性及迟发性恶心、呕吐的疗效基本相似，均可达81%～100%。本品对强致吐化疗药物顺铂的止吐疗效突出。药物相关作用饮食可略为延长本品的吸收。本品与利福平、苯巴比妥等肝酶诱导药同时使用，可加快代谢，故快代谢型者需增加剂量，慢者则不必。西咪替丁等肝酶抑制药对本品血药浓度无明显影响。适应症托烷司琼临床用于预防和治疗癌症化疗引起的恶心和呕吐。化学性质结晶，熔点201-202℃(二氯甲烷-乙酸乙酯)。单盐酸托烷司琼(TropisetronMonohydroehloride)：C17H20N2O2?HCI。[105826-92-4]。熔点283-285℃(分解)。用途有高效性和选择性的5-HT3受体拮抗剂。用于化疗所致的呕吐。用途为5-羟色胺拮抗药生产方法托品醇(I)和酰氯(Ⅱ)反应，可得托烷司琼。托烷司琼上下游产品信息上游原料托品醇下游产品