药物筛选模型研究进展-胡娟娟

:2001-06-22:(3001161940);“”(96-901-02-09)＊:1,100050,:63165184:1001-6325(2001)04-0302-04胡娟娟,杜冠华＊(,100050)Abstract:Theexperimentalmodelsfordrugscreeningareveryimportantpointsindrugdiscovery.Althoughthedrugscreeningtechniqueshavebeendeveloped,suchashighthroughputscreening(HTS),thescreeningassaymethods(models)stilllimiteddrugdiscovery.Inpresentpaper,advancedanimalmodels,cellassaysandmolecularmethodologyusedfordrugdiscoverywerereviewed.ThecharacteristicsandrequiresoftheassaymethodsusedfordrugdiscoveryinHTSwerealsodiscussed.KeyWords:drugdiscovery;assaymethods;highthroughputscreening:R965.1　　:A　　(drugscreeningmodel,drugscreen-ingassaymethod)(、),。,,。,,,、、[1]。。1　,,:、。,。1.1　,,,,,。,。。,。,,。、。,,,,、。1.2　,、,,、。,。、,302　　BasicMedicalSciencesandClinics2001.21(4),。,。,。。,1-5g(),,1/10;,,,,(),,,。,,。,,,。,,、、、,,,。1.3　、、、、、,,。,、、、,。,,[2]。,,,,,;,(),,。。2　,,。,:2.1　,;。,3。,、,。2.2　,。。,。。2.3　,,。3　,、。3.1　,,。、()。,,,,,[3～6]。,,。3032001.21(4)　　BasicMedicalSciencesandClinics。,[7]。3.2　[8],,、。,[9,10]。,,、,。,[11]。,,,。。,、,[12]。,,、,[13]。3.3　、,,。4　4.1　[14],、,,。,,,、、。、、、。,,,、[15]。[16]、、、[17]。4.2　,,。、、。,,。,。,,,。,。4.3　、[18],,、、,,,、。[19,20]。,,、。,,[21]。,,,,,,,。[22]。5　。。、、,,,,、、。,,。304　　BasicMedicalSciencesandClinics2001.21(4):[1],,,.[J].,1998,30(11):166-169.[2]CoxB,DenyerJC,BinnieA,etal.Applicationofhigh-throughputscreeningtechniquestodrugdiscovery[J].ProgMedChem,2000,37:83-133.[3]WodnickaM,GuarinoRD,HemperlyJJ,etal.Novelfluores-centtechnologyplatformforhighthroughputcytotoxicityandpro-liferationassays[J].JBiomolScreen,2000,5(3):141-152.[4],,.[J].,2000,35():44-47.[5],,,.[J].,2000,35():35-38.[6],.[J].,2000,35():21-24.[7]ShibataY,TakahashiH,IshiiY.Aconvenientinvitroscreen-ingmethodforpredictinginvivodrugmetabolicclearanceusingisolatedhepatocytessuspendedinserum[J].DrugMetabDis-pos,2000,28(12):1518-1523.[8]BuHZ,MagisL,KnuthK,etal.High-throughputcytochromeP450(CYP)inhibitionscreeningviaacassetteprobe-dosingstrategy.VI.SimultaneousevaluationofinhibitionpotentialofdrugsonhumanhepaticisozymesCYP2A6,3A4,2C9,2D6and2E1[J].RapidCommunMassSpectrom,2001,15(10):741-748.[9],,.5-HT[J].,2000,35():53-56.[10],,.A1[J].,2000,35():47-49.[11]VenkataramanS,MartinSM,SchaferFQ,etal.Detailedmethodsforthequantificationofnitricoxideinaqueoussolu-tionsusingeitheranoxygenmonitororEPR[J].FreeRadicBiolMed,2000,29(6):580-585.[12]ReesSA.Bioanalyticalstrategiestosupportadiscoveryresearchprogramme[J].JPharmBiomedAnal,1996,14:1185-1190.[13]GillmorSA,CohenFE.Newstrategiesforpharmaceuticalde-sign[J].Receptor,1993,3(3):155-163.[14]EnsleinK.Anoverviewofstructure-activityrelationshipsasanalternativetotestinginanimalsforcarcinogenicity,mutagenici-ty,dermalandeyeirritation,andacuteoraltoxicity[J].Toxi-colIndHealth,1988,4:479-498.[15]WestDB,IakougovaO,OlssonC.etal.Mousegenetics/ge-nomics:aneffectiveapproachfordrugtargetdiscoveryandvali-dation[J].MedResRev,2000,20:216-230.[16]MatternJ,BakM,HahnEW,etal.Humantumorxenograftsasmodelfordrugtesting[J].CancerMetastasisRev,1988,7:263-284.[17]JohnstonMV,TrescherWH,IshidaA,etal.Noveltreatmentsafterexperimentalbraininjury[J].SeminNeonatol,2000,5:75-86.[18]UlrichRG,BaconJA,CramerCT,etal.Culturedhepatocytesasinvestigationalmodelsforhepatictoxicity:practicalapplica-tionsindrugdiscoveryanddevelopment[J].ToxicolLett,1995,82-83:107-115.[19]RowanSJ,SandersJK.Enzymemodels:designandselection[J].CurrOpinChemBiol,1997,1:483-490.[20]HodderPS,RuzickaJ.Aflowinjectionrenewablesurfacetech-niqueforcell-baseddrugdiscoveryfunctionalassays[J].AnalChem,1999,71(6):1160-1166.[21]HarrisT.Genetics,genomics,anddrugdiscovery[J].MedResRev,2000,20:203-211.[22]ScherfU,RossDT,WalthamM,etal.Ageneexpressiondatabaseforthemolecularpharmacologyofcancer[J].NatGenet,2000,24:236-244.3052001.21(4)　　BasicMedicalSciencesandClinics