Ozanimod-RPC-1063-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOzanimodCat.No.:HY-12288CASNo.:1306760-87-1Synonyms:RPC-1063分⼦式:C₂₃H₂₄N₄O₃分⼦量:404.46作⽤靶点:LPLReceptor作⽤通路:GPCR/GProtein储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥29mg/mL(71.70mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4724mL12.3622mL24.7243mL5mM0.4945mL2.4724mL4.9449mL10mM0.2472mL1.2362mL2.4724mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.18mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.18mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Ozanimod(RPC-1063)⼀种鞘氨醇1-磷酸(S1P)受体调节剂，可⾼亲和⼒地选择性结合S1P受体亚型1(S1P1)和S1P5(S1P5)。Ozanimod对hS1P1和hS1P5受体具有调节作⽤，EC50值分别为1.03nM和8.6nM。Ozanimod可⽤于复发性多发性硬化(MS)的研究。IC50&TargetS1PR1S1PR51.03nM(EC50)8.6nM(EC50)体外研究Ozanimod(RPC-1063)haspotencyandintrinsicactivityofS1PreceptormodulatorsforS1P5acrossspecieswith[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].OzanimodrestoresthepotencywithEC50from958nMformS1P5to6.7nMformS1P5_A120TtocloselymirrortheEC50forhS1P5of8.6nMbymutatingthealanineinthemousesequence[1].OzanimodhasbindingaffinitywithKivaluesof2.0nM,59.9nMand5.6nMforhS1P5,mS1P5andmS1P5_A120T,respectively[1].Ozanimodhassaturationbindingof[3H]-ozanimodtohS1P5,andmS1P5_A120TwithKDvaluesof6.56nM,7.35nM,respectivelyandalsohassaturationbindingfor[3H]-A971432toS1P5Dvalueof8.75nM[1].体内研究Ozanimod(RPC-1063)(oralgavage;0.05,0.2,or1mg/kg;oncedaily;for14consecutivedays)exposuressufficienttoengageS1P1,butnotS1P5,resultedinreducedcirculatinglymphocytes,diseasescores,andbodyweightloss;reducedinflammation,demyelination,andapoptoticcellcountsinthespinalcord;andreducedcirculatinglevelsoftheneuronaldegenerationmarker,neurofilamentlight[1].Ozanimod(oralgavage;5mg/kg;once-daily)preventedaxonaldegradationandmyelinlossduringtoxinchallengebutdidnotfacilitateenhancedremyelinationafterintoxication[1].Ozanimod(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,aswellasattenuatedthenumber2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEofspinalcordapoptoticcells,andsignificantlyreducedthelevelsofcirculatingneurofilamentlightatthetopdoseof1mg/kg.AnimalModel:Cuprizone/RapamycinDemyelinationModel[1]Dosage:5mg/kgAdministration:oralgavage;5mg/kg;once-dailyResult:Protectedneuronalaxons,preventingbreakageandovoidformationinthecorpuscallosumofCPZ/Rapatreatedmice.SignificantlyattenuatedtheextenttowhichthecorpuscallosumdemonstratedreducedmyelincontentasvisualizedbyMRI.Didnotresultinenhancedmyelincontent.AnimalModel:C57BL/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**户使⽤本产品发表的科研⽂献•MolNeurobiol.2022Nov22.•ResearchSquarePreprint.2021Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JulieVSelkirk,etal.DeconstructingthePharmacologicalContributionofSphingosine-1PhosphateReceptorstoMouseModelsofMultipleSclerosisUsingtheSpeciesSelectivityofOzanimod,aDualModulatorofHu