L-368-899-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEL-368,899Cat.No.:HY-15008CASNo.:148927-60-0分⼦式:C₂₆H₄₂N₄O₅S₂分⼦量:554.77作⽤靶点:OxytocinReceptor作⽤通路:GPCR/GProtein储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性L-368,899⼀种⼝服有效的选择性催产素受体oxytocinreceptor拮抗剂，对⼤⿏和⼈⼦宫oxytocinreceptor的IC50值分别为8.9和26nM。L-368,899可穿过⾎脑屏障。L-368,899能抑制⼤⿏和河猴中催产素刺激的⼦宫收缩，可⽤于早产的研究。IC50&TargetIC50:8.9nM(ratuterus),26nM(humanuterus)[3].体内研究L-368,899(0.1,0.3,1mg/kg;infusedi.v.;single)showsadose-relatedantagonismofOT-stimulateduterinecontractionswithanAD50valueof0.35mg/kginvivo[1].L-368,899(3,10,30mg/kg;i.d.;single)inhibitsthecontractileeffectsofOT(AD50=7mg/kg)withalong(>4h)durationofactioninvivo(AD50:thedoseofL-368,899requiredtoreducetheresponsetoOTby50%)[1].L-368,899(10mg/kg,p.o.;single)showsbioavailability(AUC0-6h)of35%[1].L-368,899(0.54,1.8,5.4mg/kg;i.v.;single)reducesbothoxytocin-inducedandendogenousincreasesinplasmaPGFMconcentration[2].AnimalModel:AdultfemaleSprague-Dawleyrats(250-350g)[1].Dosage:0.1,0.3,1mg/kgAdministration:Infusedintravenousinjection;single.Result:InhibitedOT-stimulateduterinecontractionswithanAD50valueof0.35mg/kg.AnimalModel:AdultfemaleSprague-Dawleyrats(250-350g)[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:3,10,30mg/kgAdministration:Intraduodenal;single.Result:ExhibitedaantagonismofOT-stimulateduterinecontractionswithanAD50of7mg/kganddurationofactionmorethan4h.AnimalModel:AdultfemaleSprague-Dawleyrats(250-350g)[1].Dosage:10mg/kgAdministration:Oraladministration,single.Result:Showedorallyactivewithbioavailability(AUC0-6h)of35%.AnimalModel:MatureDorsetcrossewes(53-57kg;Removalofovaries)[2].Dosage:0.54,1.8,5.4mg/kg(3,10and30µg/kg/minfor3h;dissolvedin0.9%saline).Administration:Intravenousinfusion;single.Result:Ledtoasignificantdecreaseinboththefrequency(from2.2to1.0episodes/ewe)andamplitude(from68.8to31.8pg/mL)ofepisodesofincreasedplasmaconcentrationofPGFM.REFERENCES[1].PettiboneDJ,etal.L‐368,899,apotentorallyactiveoxytocinantagonistforpotentialuseinpretermlabor[J].Drugdevelopmentresearch,1993,30(3):129-142.[2].MannGE,etal.AttenuationofPGF2alphareleaseinewesinfusedwiththeoxytocinantagonistL-368,899.DomestAnimEndocrinol.2003Oct;25(3):255-62.[3].WilliamsPD,etal.1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo[2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperazine(L-368,899):anorallybioavailable,non-peptideoxytocinantagonistwithpotentialutilityformanagingpretermlabor.JMedChem.1994Mar4;37(5):565-71.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformed