Ozanimod-hydrochloride-RPC-1063-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOzanimodhydrochlorideCat.No.:HY-12288ACASNo.:1618636-37-5Synonyms:RPC-1063hydrochloride分?式:C??H??ClN?O?分?量:440.92作?靶點(diǎn):LPLReceptor作?通路:GPCR/GProtein儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性O(shè)zanimod(RPC-1063)hydrochloride?種鞘氨醇1-磷酸(S1P)受體調(diào)節(jié)劑，可?親和?地選擇性結(jié)合S1P受體亞型1(S1P1)和S1P5(S1P5)。Ozanimodhydrochloride對(duì)hS1P1和hS1P5受體具有調(diào)節(jié)作?，EC50值分別為1.03nM和8.6nM。Ozanimodhydrochloride可?于復(fù)發(fā)性多發(fā)性硬化(MS)的研究。IC50&TargetS1PR1S1PR51.03nM(EC50)8.6nM(EC50)體外研究Ozanimod(RPC-1063)hydrochloridehaspotencyandintrinsicactivityofS1PreceptormodulatorsforS1P5acrossspecieswith[35S]-GTPgSbinding,andtheEC50valuesof1.03nM,1.29nM,0.90nM,1.02nMand0.61nMforHumanS1P1,CynomolgusmonkeyS1P1,MouseS1P1,RatS1P1andCanineS1P1,respectively;andtheEC50valuesof8.6nM,15.9nM,957.5nM,2032.7nMand1662.0nMforHumanS1P5,CynomolgusmonkeyS1P5,MouseS1P5,RatS1P5andCanineS1P5,respectively[1].OzanimodhydrochloriderestoresthepotencywithEC50from958nMformS1P5to6.7nMformS1P5_A120TtocloselymirrortheEC50forhS1P5of8.6nMbymutatingthealanineinthemousesequence[1].OzanimodhydrochloridehasbindingaffinitywithKivaluesof2.0nM,59.9nMand5.6nMforhS1P5,mS1P5andmS1P5_A120T,respectively[1].Ozanimodhydrochloridehassaturationbindingof[3H]-ozanimodtohS1P5,andmS1P5_A120TwithKDvaluesof6.56nM,7.35nM,respectivelyandalsohassaturationbindingfor[3H]-A971432toS1P5Dvalueof8.75nM[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體內(nèi)研究Ozanimod(RPC-1063)hydrochloride(oralgavage;0.05,0.2,or1mg/kg;oncedaily;for14consecutivedays)exposuressufficienttoengageS1P1,butnotS1P5,resultedinreducedcirculatinglymphocytes,diseasescores,andbodyweightloss;reducedinflammation,demyelination,andapoptoticcellcountsinthespinalcord;andreducedcirculatinglevelsoftheneuronaldegenerationmarker,neurofilamentlight[1].Ozanimodhydrochloride(oralgavage;5mg/kg;once-daily)preventedaxonaldegradationandmyelinlossduringtoxinchallengebutdidnotfacilitateenhancedremyelinationafterintoxication[1].Ozanimodhydrochloride(oral,1or5mg/kg,for7days)hasgoodpharmacokineticsinmice[1].AnimalModel:ExperimentalAutoimmuneEncephalomyelitisModel[1]Dosage:0.05,0.2,or1mg/kgAdministration:oralgavage;0.05,0.2,or1mg/kg;oncedaily;for14consecutivedaysResult:Attenuatedbodyweightloss,terminaldiseasescoresweresignificantlyattenuatedwiththe0.2and1mg/kgdosesandALCsweresignificantlyreducedinalldosegroups.Reducedspinalcordinflammationanddemyelination,aswellasattenuatedthenumberofspinalcordapoptoticcells,andsignificantlyreducedthelevelsofcirculatingneurofilamentlightatthetopdoseof1mg/kg.AnimalModel:Cuprizone/RapamycinDemyelinationModel[1]Dosage:5mg/kgAdministration:oralgavage;5mg/kg;once-dailyResult:Protectedneuronalaxons,preventingbreakageandovoidformationinthecorpuscallosumofCPZ/Rapatreatedmice.SignificantlyattenuatedtheextenttowhichthecorpuscallosumdemonstratedreducedmyelincontentasvisualizedbyMRI.Didnotresultinenhancedmyelincontent.AnimalModel:AnimalModelC57BL/6Jmice[1]Dosage:1or5mg/kgAdministration:oral,1or5mg/kg,for7daysResult:DoseTerminalbodyweight%versusday1SpinalcordinflammationFociper20cellsSpinalcorddemyelinationScore0–5SpinalcordapoptoticcellsCountpersectionPlasmaNfLpg/mlVehicle(5%DMSO,5%Tween20,90%water)86.4±3.28.50±1.212.00±0.152.25±0.534.37±0.89Ozanimod(0.05mg/kg)85.8±2.75.00±1.03*0.91±0.21***1.08±0.23*3.53±0.46Ozanimod(0.2mg/kg)95.7±3.1*3.54±0.49***0.73±0.14***0.91±0.28*2.62±0.46Ozanimod(1mg/kg)102.8±1.8*2.67±0.56***0.33±0.14***0.60±0.19**1.91±0.34**2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ResearchSquarePreprint.2021Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JulieVSelkirk,etal.DeconstructingthePharmacologicalContributionofSphingosine-1PhosphateReceptorstoMouseModelsofMultipleSclerosisUsingtheSpeciesSelectivityofOzanimod,aDualModulatorofHumanSphingosine1-PhosphateReceptorSubtypes1and5.JPharmacolExpTher.2021Dec