>
产品中心 >
Small_molecule >
Medchemexpress/Apreplitant(同义词:MK-0869;MK-869;L-754030)/HY-10052/10mM*1mL二甲基亚砜
Description | AprepitantisaspecificNK-1Rantagonist,usedasanantiemeticagent. |
---|---|
InVitro | AprepitantdecreasesthemetabolicactivitywithanestimatedIC50valueof20µM.Aprepitantinducescell-growthinhibitionandG1cell-cyclearrest.AprepitantsignificantlyinducesapoptosisinNalm-6cells,andtheapoptosisismediatedthroughcaspase-3activation.Aprepitant(20µM)inducesp53accumulationandexpressionofpro-apoptoticp53targetgenes[2].Aprepitant(1,5,10µM)inhibitsHIVinfectioninMDMfrombothdepressedandnotdepressedHIVnegativeindividualsexvivoinadose-dependentmanner.IC90valueofaprepitantisequivalentto10μM,andtheIC50valueisabout5μM[4]. |
InVivo | AprepitantpreventstheincreaseofNK-1RexpressioninducedbyinvivoNHPinfectionwithB.burgdorferi.AprepitanttreatmentpreventsB.burgdorferi-inducedincreasesinCCL2proteinlevelsintheCSFofNHPs.AprepitanttreatmentpreventsB.burgdorferi-inducedincreasesinCCL2andCXCL13mRNAexpressioninthedorsalrootgangliaofNHPs,preventsB.burgdorferi-inducedincreasesinCCL2,CXCL13,IL-17A,andIL-6mRNAexpressioninthespinalcordofNHPs.AprepitanttreatmentattenuatesB.burgdorferiinfection-inducedreductionsinastrocyteactivity/numbers[1].Aprepitant(10mg/kg,i.p.)significantlyattenuatestheCPPexpressionandlocomotoractivationproducedbyAMPHandcocaineinmice.Incontrast,aprepitantsignificantlyenhancestheexpressionofCPPproducedbymorphinewhilesignificantlysuppressingthelocomotoractivityofthemiceconditionedwithmorphine.AprepitantdoesnotinducesignificantCPPorconditionedplaceaversionorlocomotoractivationorsuppression[3].Aprepitant(125mg/day,p.o.)resultsin1logreductioninplasmalevelsofviralRNAascomparedtonon-treatedcontrols[4]. |
ClinicalTrial | ViewMoreCollapse |
References |
|
PreparingStockSolutions |
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent. | ||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CellAssay [2] | AprepitantisdissolvedinDMSO. TheinhibitoryeffectofaprepitantonmetabolicactivityofNalm-6cellsisassessedbyuptakeofthiazolylbluetetrazoliumbromide(MTT)byviablecells.Cellsareplatedonto96-wellplatesatadensityof5000cells/well.Aftertreatmentwithaprepitantat5,10,15,20and30µMfor24,36and48h,thecellsarefurtherincubatedwith100μLofMTT(0.5mg/mL)at37°Cfor3h.Untreatedcellsaredefinedasthecontrolgroup.Followingsolubilizationofprecipitatedformazanwith100μLofDMSO,theopticaldensitometryismeasuredwithanELISAreaderatawavelengthof578nm.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. | ||||||||||||||||||||||||||
AnimalAdministration [1] | Fifteenrhesusmacaquesareanesthetizedandinoculatedintrathecallywith1×108livespiRochetesintothecisternamagna,whereasfiverhesusmacaquesareleftuninfectedandreceive1mLofRPMI1640mediumafterremovinganequivalentvolumeofCSF.TheestablishmentofinvivoB.burgdorferiinfectionisconfirmedbypositiveculturefromatleastnecropsytissuesample.Thefirstsetofanimalsarestudiedfor2weeksandincludedtwocontrolanimals(oneofwhichistreatedwithaprepitant),twoinfectedanduntreatedanimals,andtwoinfectedanimalsthataretreatedwithaprepitant.Thesecondsetofanimalsarestudiedfor4weeksandincludedthreecontrolanimals(oneofwhichistreatedwithaprepitant),fiveinfectedanduntreatedanimals,andfourinfectedanimalstreatedwithaprepitant.Animalsreceiveanaveragedoseofaprepitantof28 ± 6mg/kgperdayp.o.daily,anddrugtreatmentsarestarted2daysbeforeinoculation.ThesedosesareconsistentwithstandardveterinaryregimensforthechosendrugsinNHP,andthe4-weekdurationofthestudyprecludesthedevelopmentofneuralpathologythatoccursat8weeksfollowingB.burgdorferiinfection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. References |
|