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1、MolecularPharmacologyFastForward.PublishedonApril22,2014asdoi:10.1124/mol.113.090563MOL#90563DiscoveryandcharacterizationofaGprotein-biasedagonistthatinhibitsβ-arrestinrecruitmenttotheD2dopaminereceptorR.BenjaminFree,LaniS.Chun,AmyE.Moritz,BrittneyMiller,Tr
2、evorB.Doyle,JennieL.Conroy,AdrianPadron,JulieA.Meade,JingboXiao,XinHu,AndrésE.Dulcey,YangHan,LihuaDuan,SteveTitus,MelanieBryant-Genevier,ElenaBarnaeva,MarcFerrer,JonathanA.Javitch,ThijsBeuming,LeiShi,NoelSouthall,JuanJ.Marugan,andDavidR.SibleyMolecularNeuro
3、pharmacologySection,NationalInstituteofNeurologicalDisordersandStroke,NationalInstitutesofHealth,Bethesda,MD(RBF,LSC,AEM,BM,TDB,JLC,AP,JAM,DRS)NationalCenterforAdvancingTranslationalSciences,NationalInstitutesofHealth,Rockville,MD(JX,XH,AED,ST,MBG,EB,MF,NS,
4、JJM)CenterforMolecularRecognitionandDepartmentsofPsychiatryandPharmacology,ColumbiaUniversityCollegeofPhysiciansandSurgeons,NewYork,NY.DivisionofMolecularTherapeutics,NewYorkStatePsychiatricInstitute,NewYork,NY(YH,LD,JAJ)SchrödingerInc.,NewYork,NY(TB)Depart
5、mentofPhysiologyandBiophysicsandInstituteforComputationalBiomedicine,WeillMedicalCollegeofCornellUniversity,NewYork,NY(LS)1Copyright2014bytheAmericanSocietyforPharmacologyandExperimentalTherapeutics.MOL#90563RunningTitle:GProtein-BiasedD2ReceptorAgonistCorr
6、espondingAuthor:R.BenjaminFree,Ph.D.MolecularNeuropharmacologySectionNationalInstituteofNeurologicalDisordersandStroke,NationalInstitutesofHealth5625FishersLane,Room4S-04Bethesda,MD20892-9405phone:301-443-4785fax:301-480-3726email:freeb@ninds.nih.govTextPag
7、es:14Tables:2Figures:4References:41AbstractWords:245IntroductionWords:738ResultsandDiscussionWords:1945Abbreviations:D1R:D1dopaminereceptor,D2R:D2dopaminereceptor,D3R:D3dopaminereceptor,D4R:D4dopaminereceptor,D5R:D5dopaminereceptor,EC50:50%excitatoryconcent
8、ration,IC50:50%inhibitoryconcentration2MOL#90563ABSTRACTAhigh-throughputscreeningcampaignwasconductedtointerrogatea380,000+smallmoleculelibraryfornovelD2dopaminereceptormodulatorsusingacalciummobilizat
