[21]MCKEAGEK,CROOMKF.Decitabine:inmyelodysplasticsyndromes[J].Drugs,2006,66(7):95129581[22]YEEKW,JABBOURE,KANTARJIANHM,etal.Clinicalex2periencewithdecitabineinNorthAmericanpatientswithmyelo2dysplasticsyndrome[J].AnnHematol,2005,84(Suppl13):18224.[23]SABAHI,WIJERMANSPW.Decitabineinmyelodysplasticsyndromes[J].SeminHematol,2005,42(3Suppl2):23231.[24]KOSHYM,DORNL,BRESSLERL,etal122Deoxy52azacyti2dineandfetalhemoglobininductioninsicklecellanemia[J].Blood,2000,96(7):237922384.[25]JOSEPHD,MABELK,LOUISED,etal.Maintenanceofelevat2edfetalhemoglobinlevelsbydecitabineduringdoseintervaltreat2mentofsicklecellanemia[J].Blood,2002,99(11):390523908.[26]SAUNTHARAJAHY,HILLERYCA,LAVELLEeD,etal1Effectsof52aza222deoxycytidineonfetalhemoglobinlevels,redcelladhesion,andhematopoieticdifferentiationinpatientswithsicklecelldisease[J].Blood,2003,102(12):386523870.[27]HASSANAF,GEORGEFA.Inductionoffetalhemoglobininthetreatmentofsicklecelldisease[J].Hematology,2006,2006(1):58262.[28]ISSAJP,GHARIBYANV,CORTESJ,etal.PhaseIIstudyoflow2dosedecitabineinpatientswithchronicmyelogenousleukemi2aresistanttoimatinibmesylate[J].JClinOncol,2005,23(17):394823956.[29]KANTARJIANHM,OBRIENS,CORTESJ,etal1Resultsofdecitabine(52aza222deoxycytidine)therapyin130patientswithchronicmyelogenousleukemia[J].Cancer,2003,98(3):5222528.[30]LUBBERTM,MINDENM.Decitabineinacutemyeloidleukemia[J].SeminHematol,2005,42(3Suppl2):38242.[31]SCHRUMPDS,FISCHETTEMR,NGUYENDM.PhaseIstudyofdecitabine2mediatedgeneexpressioninpatientswithcancersinvolvingthelungs,esophagus,orpleura[J].ClinCancerRes,2006,12(19):577725785.[32]GOLLOBJA,SCIAMBICJ,PETERSONBL,etal.PhaseItri2alofsequentiallow2dose52aza222deoxycytidineplushighdoseintravenousbolusinterleukin22inpatientswithmelanomaorrenalcellcarcinoma[J].ClinCancerRes,2006,12(15):461924627.[33]POHLMANNP,DILEONELP,CANCELLAAI,etal.PhaseIItrialofcisplatinplusdecitabine,anewDNAhypomethylatinga2gent,inpatientswithadvancedsquamouscellcarcinomaofthecervix[J].AmJClinOncol,2002,25(5):4962501.[34]MOMPARLERRL,AYOUBJ.Potentialof52aza222deoxycyti2dine(Decitabine)apotentinhibitorofDNAmethylationforther2apyofadvancednon2smallcelllungcancer[J].LungCancer,2001,34(Suppl4):1112115.[35]SCHWARTSMANNG,SCHUNEMANNH,GORINICN,etal.AphaseItrialofcisplatinplusdecitabine,anewDNA2hypom2ethylatingagent,inpatientswithadvancedsolidtumorsandafol2low2upearlyphaseIIevaluationinpatientswithinoperablenon2smallcelllungcancer[J].InvestNewDrugs,2000,18(1):83291.[36]DacogenTM(decitabine)forInjection[EB/OL]12006(2006212208)1[37]HURTUBISEA,MOMPARLERRL.Effectofhistonedeacety2laseinhibitorLAQ824onantineoplasticactionof52Aza222deoxy2cytidine(decitabine)onhumanbreastcarcinomacells[J].CancerChemotherPharmacol,2006,58(5):6182625.(:2007201229):863(2004AA2Z3782);(2006DFA31420);(0630073):,,3:,,,Tel:(010)63165184E2mail:dugh@imm1ac1cn,3(,100050):,,,,,:;;:R96:A:1001-2494(2008)02-0084-05,,,,,[122][3],,,,,,,,,,48ChinPharmJ,2008January,Vol143No1220081432,,[425]1:,:2000,1536,34569600[6](uHTS),,[2]:,,[728],[9]:,,,[10]:,,,2,,,,,,G2(GPCR)211,,,,,(epi2somalvector),,212,,[11],(luciferase)2,(GFP),,,,GFPGFP,,2,,,[12214]2,(FRET)CCF4/AM,,[7]213,,,,,,,21311(fluorescencepolarization,FP)FP,2[15]FP,,,,,,GPCRHTS[16217]Linda2(CRF2R)cAMP[8]21312(fluorescenceresonanceenergytransfer,FRET)FRET,,,,[8]2(2lactamase)FRET,CCF4,72(fluorescein),,530nm,,,2lactamase,2lactamase,FRET,460nm[9]GPCR2(hO2TR)[18220]FRET[19]21313(timeresolved2fluores2cenceresonanceenergytransfer,TREForTR2FRET)TREF,TREF,,,Hugo[20],XL665()25820081432ChinPharmJ,2008January,Vol143No12214(fluorescenceimaging)21411(highcontentscreening,HCS),,,,,:,(),HCS,GPCR,,,,,[2,12]Gurwitz[21]HCS17,CellCardTM(multiplexed)HCS,VitraBioscience,96,,,[22]CellCardCarrier,96CellCard,,,[9],[23]21412(fluorescenceconfocalmicro2scopeimaging),,,,EVOscreen,,[24](FRET),(fluorescencelifetimeimagingmi2croscopy,FLIM),FRAP(fluorescentrecov2eryafterphotobleaching),FLIP(fluorescencelossinphotobleaching),FCS(fluorescencecorrelationspectros2copy)[13]21413(fluorescencecorrelationspectroscopy,FCS)FCS,,,,FCS,,,FCS[2,17]OLEGFCSGPCR,3456,2L[7]21414FLIPR(fluorescentimagingplatereader)FlIPR96FLIPR384MolecularDevices,,,,FLIPR,pH,,CCD,,Fluo23/AMcal2ciumgreen[25]21415FMATTM(fluometricmicrovolumeassaytechnology)PEBiosystem,Cy5,633nm/,,,FMAT,GPCR,,2,2FMATELISAFLISA,Biosignalamplifiedluminescentproximityhomogeneousassayscreen(AlphaScreenTM),AmershamImagingResearchIncLEADseekerTMHomogeneousImagingsystem,(SPA),SPA10,SurfacePlasmonResonance(SPR),CLIPRsystem(ChemiluminescenceImagingPlateReader),3,,GPCR,Transf2lourm,GPCR(Gi,Gs,Gq,G12/13),GPCRGG,,(adaptor)Ar2restin,GPCR,Ar2restin,GPCRGAr2restins,,(Resensi2tization)Arrestin,,Arrestin,GPCR,,,,GPCR68ChinPharmJ,2008January,Vol143No1220081432,Richik[26]GFPArrestinsU2OSV2RYu[27]2GPCRArrestins2CXCR2GPCR,FLIPR,(cAMP)FPBRET[28229],,,Ausseil[30],42,2,Tian[31]FRET,Hela,,3(caspase3),,,4,,,,,,,,[32],,MultiplexedHCS,MultiplexedHCS,,,[33],,,,,,,,,,,,REFERENCES[1]DUGH1Strategyofdrugdevelopmentandapplicationofhighthroughputscreeni[J]1Chin