MOR-modulator-1-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMORmodulator-1Cat.No.:HY-170437CASNo.:2976336-81-7分⼦式:C₂₄H₂₇N₃O₄S分⼦量:453.55作⽤靶点:OpioidReceptor作⽤通路:GPCR/GProtein;NeuronalSignaling储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性MORmodulator-1(compound6)⼀种有效且选择性的μ阿⽚受体(MOR)调节剂。与NAT(6α-configuration)相⽐，MORmodulator-1表现出改阿⽚受体选择性，增强体内拮抗作⽤，并且总体上减少了戒断症状。MORmodulator-1与羧酰胺连接⼦μ，δ，γ连接，Ki分别为0.25,41.1,1.30nM。IC50&TargetμOpioidReceptor/MORκOpioidReceptor/KORδOpioidReceptor/DOR0.25nM(Ki)1.3nM(Ki)41.1nM(Ki)体外研究MORmodulator-1exhibitssubnanomolarbindingaffinityattheMOR,singledigitnanomolarbindingaffinityattheKOR(kappaopioidreceptor),andmuchlowerbindingaffinitytotheDOR(deltaopioidreceptor),preservingreasonableselectivityattheMORovertheDOR[1].MORmodulator-1displaysthehighestδ/μselectivity,whichisabout3-foldhigherthanthatofNAT[1].MORmodulator-1linkswithcarboxamidolinkerμ,δ,γwithKiof0.25,41.1,1.30nM,respectively[1].MORmodulator-1bindswithMOR[35S]GTPγSwithanEC50of2.16nM[1].MORmodulator-1bindswithKOR[35S]GTPγSandDOR[35S]GTPγSwithanEC50of3.83and23.6nM,respectively[1].MORmodulator-1showsnanomolartosubnanomolarpotencyandconsiderablylowefficacywith%Emaxvaluesof11.3[1].MORmodulator-1significantlyantagonizesDAMGOinducedintracellularcalciumincreaseinGαqi5-transfectedmMORCHOcells[1].MORmodulator-1inhibitscalciumwithanIC50of5.64nMinGαqi5-transfectedmMORCHOcells[1].体内研究MORmodulator-1(10mg/kg,warm-watertailimmersion,20min)containinga2’-thiazolylmoietyactsasthemostpotentmemberinthisseriesofNATanalogsinantagonizingmorphinemediatedantinociceptioneffect1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].MORmodulator-1(10mg/kg,warm-watertailimmersion,20min)showsAD50valueof0.043mg/kg,10timesmorepotentcomparedtoNAT[1].MORmodulator-1(10mg/kg,warm-watertailimmersion,20min)standsoutasthemostactiveexpoxymorphinan-basedmoleculeamongallMORmodulators[1].MORmodulator-1(0.05-10mg/kg,s.c.,20min)exhibitsfewerwetdogshakesandpawtremorsatalltestingdosesthan1mg/kgnaloxone(NLX),evenatthehighestdosesof5mg/kgand10mg/kg,respectively[1].MORmodulator-1(5mg/kg,s.c.,20min)meancountvaluesinwetdogshake,jumpsandpawtremorsare9.8,36.8and30.2,respectively[1].MORmodulator-1inbrainat5,10,and30minafteradministrationwere0.187,0.235,and0.264μg/g,respectively,revealingthatMORmodulator-1quicklypenetratedintothebrainafters.c.administrationandremainedinthebrainforalongtime[1].REFERENCES[1].HuangB,etal.Discoveryof6α-ThiazolylcarboxamidonaltrexamineDerivative(NTZ)asaPotentandCentralNervousSystemPenetrantOpioidReceptorModulatorwithDrug-likePropertiesforPotentialTreatmentofOpioidUseDisorder.ACSPharmacolTranslSci.2024Dec5;7(12):4165-4182.McePdfHeightCaution:Producthasnotbeenfullyvalidat