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上講小結(jié)2022/10/151上講小結(jié)2022/10/111人類基因組計劃藥物靶點Lead藥物HitHTS,化學(xué)合成(盲篩、效率低下)分子生物學(xué)結(jié)構(gòu)生物學(xué)靶標(biāo)結(jié)構(gòu)計算機輔助藥物設(shè)計化學(xué)合成/HTS效率高藥物設(shè)計高通量篩選技術(shù)關(guān)鍵2022/10/152人類基因組藥物靶點Lead藥物HitHTS,化學(xué)合成分子生物第二章、藥物設(shè)計和篩選中國科學(xué)院上海藥物研究所“藥物發(fā)現(xiàn)與設(shè)計中心”
沈旭2022/10/153第二章、藥物設(shè)計和篩選中國科學(xué)院上海藥物研究所沈旭202藥物篩選在新藥發(fā)現(xiàn)中的地位藥物篩選的常見重要方法(結(jié)合本實驗室工作)重要疾病治療藥物篩選方法舉例展望
虛擬篩選技術(shù)(計算機科學(xué))生物物理化學(xué)技術(shù)、組合化學(xué)分子細(xì)胞生物學(xué)天然產(chǎn)物化學(xué)(中草藥資源)(后基因組時代藥物篩選新模式)2022/10/154藥物篩選在新藥發(fā)現(xiàn)中的地位2022/10/114新藥篩選基本方法一、隨機篩選最經(jīng)典篩選方式。曾發(fā)揮重要作用,50~60年代較為變通。它用一個或多種生物試驗手段評篩化合物或自然資源?,F(xiàn)在應(yīng)用的許多有效治療藥物都是通過隨機篩選得到的隨機篩選典型代表細(xì)菌培養(yǎng)法
從自然資源中篩選抗菌素;瘤株細(xì)胞培養(yǎng)法
從多種來源的化學(xué)物質(zhì)中篩選抗癌藥物;70年代后利用受體(競爭)結(jié)合法隨機篩選神經(jīng)-精神性藥物等。2022/10/155新藥篩選基本方法一、隨機篩選2022/10/115隨機篩選遭到冷落,新藥研制部門特別是藥物產(chǎn)業(yè)部門很少依靠隨機篩選做為發(fā)現(xiàn)新藥的主要手段2022/10/156隨機篩選遭到冷落,新藥研制部門特別是藥物產(chǎn)業(yè)部門很少依靠隨機二、經(jīng)驗式重復(fù)篩選使用最為廣泛的傳統(tǒng)的篩選方法主要特點:合成篩選緊密配合,經(jīng)重復(fù)性(trialanderror)試驗過程,根據(jù)構(gòu)效關(guān)系(SAR),不斷對化合物進(jìn)行結(jié)構(gòu)修飾(structuralmodification),找到選擇性導(dǎo)向或候選化合物。屬于定向合成與篩選,成敗的關(guān)鍵在于確定適當(dāng)篩選目標(biāo)和范圍,選好靶標(biāo)(target)和篩選指標(biāo)。2022/10/157二、經(jīng)驗式重復(fù)篩選使用最為廣泛的傳統(tǒng)的篩選方法2022/1除去抗感染、抗病毒和抗寄生蟲類藥物以外,制藥工業(yè)用來做為藥物靶向篩選的靶標(biāo)已有417種,包括受體、酶、離子通道等,涉及10個系統(tǒng)的功能(表)。在人類基因組計劃完成后這種靶標(biāo)可增至3000-4000個。據(jù)統(tǒng)計,人類疾病有30,000種,但藥物能控制和改善的只有100-150種。未得到控制和改善的疾病大多數(shù)與基因有關(guān),每一種疾病大約涉及5-10個基因。因此,靶向篩選是新藥篩選的一個很有發(fā)展?jié)摿Φ闹匾较蚝皖I(lǐng)域。(后基因組時代藥物發(fā)展新模式)2022/10/158除去抗感染、抗病毒和抗寄生蟲類藥物以外,制藥工業(yè)2022/1三、藥物合理設(shè)計與篩選基于結(jié)構(gòu)的藥物設(shè)計與篩選(structure-baseddrugdesignandscreening)將基于機制的篩選與藥物合理設(shè)計融合為一體,為了進(jìn)行藥物合理設(shè)計,必須獲得靶標(biāo)大分子的結(jié)構(gòu),特別是三維結(jié)構(gòu)的信息。因此,該種篩選策略的第一步是靶標(biāo)的分子結(jié)構(gòu)分析。在實施中也可取已知三維結(jié)構(gòu)的靶標(biāo),直接進(jìn)行藥物合理設(shè)計,做為工作的起始點。如果大分子一級結(jié)構(gòu)已知,三維結(jié)構(gòu)尚水闡明者,可根據(jù)同源蛋白模建等方法預(yù)測其三維結(jié)構(gòu)。大分子一級結(jié)構(gòu)不清,只有配體結(jié)構(gòu)信息的,根據(jù)其配體推導(dǎo)藥效基因(pharmacophore)模型,或提出假想受體,間接設(shè)計化合物。理論計算-藥物設(shè)計-化學(xué)合成-生物篩選密切配合成功的藥物合理設(shè)計可大量減少化學(xué)合成和生物篩選的工作量,提高新藥發(fā)現(xiàn)的機率,降低基金投入。2022/10/159三、藥物合理設(shè)計與篩選基于結(jié)構(gòu)的藥物設(shè)計與篩選2022/10“計算機虛擬篩選”與“高通量篩選”技術(shù)完美結(jié)合大大加速了新藥發(fā)現(xiàn)進(jìn)程2022/10/1510“計算機虛擬篩選”與“高通量篩選”技術(shù)2022/10/111
臨床前研究
臨床研究新藥Summary:藥物篩選分子生物學(xué)、結(jié)構(gòu)生物學(xué)、基因組、蛋白質(zhì)組、組合化學(xué)、高通量篩選、計算機輔助藥物設(shè)計、生物信息學(xué)與化學(xué)信息學(xué)(數(shù)據(jù)庫學(xué))、化學(xué)生物學(xué)化合物
藥物發(fā)現(xiàn)2022/10/1511臨床前研究臨床研究新藥SummaII、藥物篩選Hits
ScreenLeads
Pre-clinicDevelopmentClinicalDevelopmentScreenParadigmBlock-busterDrugs2022/10/1512II、藥物篩選HitsScreenLeadsPre-cl2022/10/15132022/10/1113BiologicalTargetSelectionAssayReagentsAssayDevelopmentAndOptimizationAssayTransferAssessmentScreenDevelopmentAndValidationScreenAutomationAndOptimizationScreeningCompoundDeckLeadGenerationScreenParadigmHTS,uHTSScreenPlatforms2022/10/1514BiologicalTargetAssayReagen高通量篩選技術(shù)(High-ThroughputScreen,HTS)2022/10/1515高通量篩選技術(shù)2022/10/11152022/10/15162022/10/11162022/10/15172022/10/11172022/10/15182022/10/11182022/10/15192022/10/11192022/10/15202022/10/11202022/10/15212022/10/1121(tobecontinued)2022/10/1522(tobecontinued)2022/10/1122(continued)2022/10/1523(continued)2022/10/1123III、篩選平臺Beingfamiliarwithvariousscreenplatformswillbeinanadvantageouspositiontoevaluatethebestassayforthetargetscreeningwiththeidentificationofatarget.(靶標(biāo))Understandingvariousscreenplatformswillhelpinarrivingatthebestscreenswiththeavailableequipmentandreagents.(設(shè)備和化合物)2022/10/1524III、篩選平臺BeingfamiliarwithvaTargetsReagentsandplatereadersavailability
AssayDesign2022/10/1525TargetsReagentsandplateAssa1、Assayformats20世紀(jì)70年代:低通量和單一試管篩選方法;現(xiàn)在:(1)多孔板篩選(96-、384-、1536-,3456-,9600孔板篩選技術(shù)相繼出現(xiàn))(2)平板讀數(shù)(platereaders)技術(shù):熒光、發(fā)光、閃爍等檢測技術(shù)的發(fā)展。
Stackersholdingseveralplates(10-40plates).2022/10/15261、Assayformats20世紀(jì)70年代:低通量和單Biacore3000,96BiacoreS51,384962022/10/1527Biacore3000,96BiacoreS51,382.Assaytechniques依據(jù):激活或抑制、激動劑(activator)、抑制劑inhibitor方法:(1)體外篩選(invitro)(酶活、受體結(jié)合)(cell-free)(2)細(xì)胞水平(cell-based)(Heterogeneous&Homogeneoustypes)2022/10/15282.Assaytechniques依據(jù):激活或抑制、激3、體外(invitro)篩選(cellfree)采用系統(tǒng)簡單或復(fù)雜(酶反應(yīng)、蛋白-蛋白相互作用、膜受體-配體結(jié)合、可溶性受體-配體結(jié)合檢測實驗)特點
a、被篩化合物易于直接作用于靶標(biāo);b、目標(biāo)化合物作用靶標(biāo)明確;c、明確的作用機理;d、易于發(fā)展便宜易得的靶標(biāo)模型;e、適應(yīng)新技術(shù)的發(fā)展,易于自動化。2022/10/15293、體外(invitro)篩選(cellfree)采Invitrocell-freebiochemicalassaysHomogeneousHeterogeneousRadioactiveassaysSPAbeadSPAplateCell-freeBiochemicalAssaysChromogenicassaysNon-radioactiveassaysAbsorbanceassaysFluorescenceassaysBeadbasedassaysRadioactiveassaysNon-radioactiveassaysFiltrationassaysAdsorptionassaysPrecipitationassaysRadioimmunoassaysELISAassays2022/10/1530Invitrocell-freebiochemicalA.HeterogeneousAssays多步篩選方法multipleadditions/incubations/washings/transfers/filtrations/readingsofthesignal特點Laborintensive,complicatedstep,hardtoautomate2022/10/1531A.HeterogeneousAssays多步篩選方法(1)NonradioactiveHeterogeneousAssaysEnzymeimmunoassays(widelyusedinvitroassays)ELISA(EnzymeLinkedImmunosorbentAssay)酶聯(lián)免疫吸附試驗AnELISAplateAnHIVELISA,sometimescalledanHIVenzymeimmunoassay
(EIA)isthefirstandmostbasictesttodetermineifanindividualispositiveforaselectedpathogen,suchasHIV.Thetestisperformedina8cmx12cmplasticplatewhichcontainsan8x12matrix
of96wells,eachofwhichisabout1cmhighand0.7cmindiameter.
2022/10/1532(1)NonradioactiveHeterogeneouPositiveELISATestNegativeELISATest
HIVantigenspre-coatedontoanELISAplatePatientserumcontainingantibodies.IfthepatientisHIV+,thenthisserumwillcontainantibodiestoHIV,andthoseantibodieswillbindtotheHIVantigensontheplate.
Anti-humanimmunoglobulincoupledtoanenzyme.Thisisthesecondantibody,anditbindstohumanantibodies.
Chromogenorsubstratewhichchangescolorwhencleavedbytheenzymeattachedtothesecondantibody.2022/10/1533PositiveELISATestNegativeELSEPAntibodyAntibody-2colour,fluorescence,chemiluminescenceInhibitorScreeningSSubstrateEEnzymePProductELISA方法藥物篩選原理Read!EGFR抑制劑篩選ELISA試劑盒2022/10/1534SEPAntibodyAntibody-2colour,f(2)RadioactiveHeterogeneousAssaysVerycommonlyused,highlysensitiveandrobustdespitehandlinghazardsandradioactivewastegeneration分離放射性產(chǎn)物的一般方法RadioactiveProductRadioactiveSubstractGlass-fiberfilters(filtration)WashingDryingatrt.TransferredintoavialaddscintillantCountedinascintillationcountera.FiltrationAssays2022/10/1535(2)RadioactiveHeterogeneousAb.AdsorptionAssaysInproteinkinasereactionsthephosphorylatedproduct(acidic)byionicinteractioniscapturedonphosphocell-ulose(磷酸纖維素)filters;filterwashed,air-driedandtransferredintoavial;scintillantisadded,andthevialiscountedinascintillationcounter.c.PrecipitationAssaysInthetraditionalenzymeassays,theradiolabelfromthesubstrateistransferredtoaproteinacceptor,andtheradiolabeledproductisisolatedbyprecipitationwithtrichloroaceticacid(TCA);theprecipitateiscollectedbyfiltrationandwashing,thefilteristransferredintoaviral,andtheviraliscountedaftertheadditionofscintillant.2022/10/1536b.AdsorptionAssaysInproteind.Radioimmunoassays(RIA)Aclassicalmethodformeasuring:hormones,ligandsandotherbiomolecules.抗原對其抗體進(jìn)行免疫結(jié)合進(jìn)行的分析通常的抗原是指人體內(nèi)存在的激素,酶,小分子和多肽,特異蛋白等。對于其它動物,即異體物質(zhì),一旦把這些物質(zhì)引入動物體內(nèi),其免疫系統(tǒng)就會作出反應(yīng),產(chǎn)生出專一結(jié)合抗原的抗體(即免疫球蛋白)。抗原和抗體的反應(yīng)是一一對應(yīng)的,高度精密專一的。
2022/10/1537d.Radioimmunoassays(RIA)AclaB.HomogeneousAssaysOne-potassayswithnotransferorwashstepsAllthereagentsareaddedinonesteporinmultistepsThesignalisreadinaplatereader(1)RadioactiveHomogeneousAssaysBasedonscintillationproximityassay(SPA)(親近閃爍檢測)witheitherSPRbeadsorscintillant-coatedplates.Scintillationproximityassay(SPA),aninnovativeapproachforhigh-throughputscreeningintroducedin1991,allowstherapidandsensitiveassayofawidevarietyofmolecularinteractionsinahomogeneoussystem.SPAisquickandversatileand,asaresult,isnowbeingusedinthehigh-throughputscreening(HTS)laboratoriesofover60companiesworldwideastherecognizedindustrygoldstandard.2022/10/1538B.HomogeneousAssaysOne-pot2022/10/15392022/10/11392022/10/15402022/10/11402022/10/15412022/10/11412022/10/15422022/10/11422022/10/15432022/10/11432022/10/15442022/10/1144(2)NonradioactiveHomogeneousAssaysA.ChromogenicAssayschromophoreSubstrate(colorless)Substrate(color)max
Enzymee.g.Inthe-glucuronidase(葡糖苷酸酶)assay,thesubstratep-nitro-phenyl-glucuronide(葡糖苷酸)iscolorless,butthep-nitrophenolformedinthereactionunderalkalineconditionsiscolor-ed,andabsorbanceat415nmismeasured.2022/10/1545(2)NonradioactiveHomogeneousB.AbsorbanceAssaysInsomereactions,thoughneitherthereactionsubstratenortheproducthasUVabsorbance,thesubstrateorproductcouldbecoupledtoanotherenzymeassaythatcanbemonitoredbyabsorbance.
EnzymeassaySubstrateproductabsorbslightintheUV/NoNo/absorbslightintheUV2022/10/1546B.AbsorbanceAssaysInsomereC.FluorescenceAssays100to1000timesmoresensitivethancolorimericorspectrophotometricassays.PopularnonradioactivemethodsforHTSwiththeavailabilityof96-,384-wellplatereaders.2022/10/1547C.FluorescenceAssays100to12022/10/15482022/10/11482022/10/15492022/10/11492022/10/15502022/10/1150FluorescenceintensityassaysFluorogenicassays(CBP+PPAR)Fluorescencequenchassays(CypA+L)2022/10/1551FluorescenceintensityassaysFFluorogenicassays
(CBP+PPAR)2022/10/1552Fluorogenicassays2022/10/1152CPAmax
(410nm)PPARLigandCPAPPARmax
(410nm)2022/10/1553CPAmaxPPARLigandCPAPPARmacis-Parinaricacid2022/10/1554cis-Parinaricacid2022/10/1154Fluorescencequenchassays
(CypA+Ligand)2022/10/1555Fluorescencequenchassays202隨著DDDC838濃度增大,CypA熒光值下降,實驗中,CypA濃度保持為4M,其中化合物DDC838濃度:a,0M;b,1M;c,2M;d,4M;e,8M;f,16M;g,32M。)
2022/10/1556隨著DDDC838濃度增大,CypA熒光值下降,實驗中,Cy(ii)Fluorescencepolarization(FP)FPmeasurementsprovideinformationonmolecularorientationandmobilityandprocessesthatmodulatethem,includingreceptor–ligandinteractions,proteolysis,protein–DNAinteractions,membranefluidityandmusclecontraction.2022/10/1557(ii)Fluorescencepolarization2022/10/15582022/10/1158TheFPassayscanbeclassifiedintothefollowingthreedifferentmodes:1a.IncreaseinsizeMacromoleculeMacromoleculeFPSignalincreaseMacromoleculeMacromoleculeFPSignaldecrease1b.Competition2022/10/1559TheFPassayscanbeclassifie2.DecreaseinsizeFPsignaldecrease3a.DirectImmunoassayPPFPsignalincrease3b.CompetitionImmunoassayPPFPsignaldecrease2022/10/15602.DecreaseinsizeFPsignal(ii)Fluorescenceresonanceenergytransfer(FRET)
(熒光共振能量傳遞)
assays(iii)Homogeneoustime-resolvedfluorescence(HTRF)/Time-resolvedFRET(iv)Fluorescencecorrelationspectroscopy(FCS)(熒光相干光譜學(xué))(v)Fluorescencelifetimespectroscopy(FLS)2022/10/1561(ii)Fluorescenceresonanceen2022/10/15622022/10/11622022/10/15632022/10/11632022/10/15642022/10/11642022/10/15652022/10/11652022/10/15662022/10/11662022/10/15672022/10/11674、Cell-basedassaysMimictheenvironmentofalivingcell;Usedforconfirmationofleadscomingprimaryinvitrobiochemicalscreens;Usedfortargetswherebiochemicalassaysarenotavailable;Giveinformationaboutcellularinteractionswiththetargetandshedlightonthestabilityofcompounds.Traditionally,lowormediumthroughputduetothecumbersomestepsinvolved.Nowadays,HTSforprimaryscreening.HeterogeneousandHomogeneousassays2022/10/15684、Cell-basedassaysMimictheeCellbasedassayHomogeneousassaysHeterogeneousassaysMicrobe-basedassaysMammalianCell-basedassaysRescuetypeassaysGrowth/noGrowthassaysTwo-hybridassaysReporterassaysRadioactiveassaysNonradioactiveFunctionalassaysReporterassaysMiscellaneousassaysRadioactiveassaysFiltrationassaysRadioimmuno-assaysCytotoxicity/CellproliferationassaysNonradioactiveassaysELISAassaysCellbasedassay2022/10/1569CellbasedassayHomogeneousasA.HeterogeneousAssays1.ELISAAssaysNonradioactiveassaysaremainlyELISAassys.Cellsaretreatedwithcompounds,andthecellularchangesareassayedbyELISAassays.2.RadioactiveAssaysTheassaysinvolvingradioisotopesaregenerallylimitedtoreceptor-bindingassaysandquantitationofbiomoleculeslikehormonesincellextractsbyradioimmunoassays.Filtration,Radioimmunoassays,CellProliferation2022/10/1570A.HeterogeneousAssays1.ELISB.HomogeneousAssaysThehomogeneouscell-basedassayscanbedoneinmicrobes,yeast,ormammaliancells.Theseassaysconsistofgrowingthecells,treatmentofthecellswithcompound,anddevelopingandreadingthesignal.Thehomogeneouscell-basedassayreferstotheassayinasinglestepormultiplestepadditionsinthesamewellofamicrotiterplate.2022/10/1571B.HomogeneousAssaysThehomog1、Microbe-BasedAssaysFindantibacterialagentsandcytotoxicanticanceragents.Inclusionbody,posttranslationalmodificationcheap,simplea.AntibacterialactivitycompoundsInhibitionzoneTheseassayshavebeenautomatedwithrobotsundersterileenvironmentinmajorPharma.2022/10/15721、Microbe-BasedAssaysFindantb.Growth/NogrowthassaysWithfunctionalexpressionofhomologousorheterologoustargetsinmicrobialsystems,renderingthecelldependentonthetargetexpressed,agrowthornogrowth(ofthemicrobe)typeofscreencanbedeveloped.c.Reporter-basedassaysAtargetproteiniscoupledtoapromoter(transcriptionalfactor)thatinturniscoupledtoareceptorproteinlike-galactosidase,luciferase,orchloramphenicolacetyltransferase.ThusatargetproteinisengineeredintheextracellulardomainoftheToxRproteininE.coli.Whencompoundsbindtothetargetprotein,promotedimerizationofextracellulardomainofhybridToxRprotein,whichactivatesthetoxRpromoterandconsequentlyactivatestheexpressionofreporterandcanbeeasilyreadinaplatereader.2022/10/1573b.Growth/NogrowthassaysWithd.YeastExpressionAsyeastoffersnullbackgroundforhumanreceptors,humanGPCRsalongwithappropriatemammalianG-proteinscanbeexpressedinyeastcoupledtothepheromonesignalingpathway(信息素傳導(dǎo)途徑)toscreenforagonistsandantagonists.e.Two-hybridYeastsystemProtein-proteinexpression2022/10/1574d.YeastExpressionAsyeastof2、MammalianCell-BasedAssaysCell-basedassaysdifferfrommoretraditionalscreeningenzyme-orantibody-basedassaysinthattheuseoflivecellsrequiresspecialconsiderations.
a/freeofmycoplasma(支原體);b/cellsfromfrozenstockshouldbeviablewithoutalterationinthegrowthcurve;c/targetproteinshouldbeexpressedatahighenoughlevelinthecells;d/littlefluctuationinreplicates…….
Cell-basedassayswilltakeseveraldaysbeforeinitiationoftheassays.Thereadoutsofhomogeneousformatareradioactive,luminescence,orfluorescence.2022/10/15752、MammalianCell-BasedAssaysC1).RadioactiveAssaysCell-basedradioactivehomogeneousassayshavebeenusedforfunctionalassaysandreceptor-ligandassays.ReceptorbindingassaysReceptorbindingassayswithmembranereceptorscanalsobeassayswithwholecells,eitheradherentorsuspensioncells,witharadioligand.GTP--Sbindingassays,Signaltransductionassays2022/10/15761).RadioactiveAssaysCell-bas2).NonradioactiveAssaysCyclicAMPassaysAhighefficiencyfluorescencepolarization(HEFP)cAMPassayisahomogenouscAMPassaythatcanmeasurecAMPlevelsinwholecellsandisbasedoncompetitionbetweencAMPproducedinthecellandexogeneouslyaddedfluorescentcAMPastrancer(LJLBioSystems)2022/10/15772).NonradioactiveAssaysCycliCell
Incubated
CellLysedDrugFluorescenttrancercAMP-specificantibodyFPsignalmeasurement2022/10/1578CellIncubatedCellDrugFluores3).Reporter-basedAssaysMostofthetranscriptionfactorsaremodular,consistingofaDNA-bindingdomainandactivationdomain.Thesedomainscanbeinterchangedbetweendifferentfactorsandstillretaintheirfunctionalproperties.Areportergeneconstructconsistsofaninducibletrans-criptionalcontrolelementdrivingtheexpressionofareportergene.Reportergenescodeforproteinsthatpossessuniqueenzymeactivities,andtheactivityassaysareadaptabletoHTS.2022/10/15793).Reporter-basedAssaysMostRARRXRLBDDBDRARETTNPBLG268AGGTCAAGGTCAAGGTCADR1DR15`3`DR1LacZReportergeneSRC-1:LXXLLClampExperimentalmodelofRAR-RXRheterodimers:RARE:biotinylatedretinoic-acid-responseelement2022/10/1580RARRXRLBDDBDRARETTNPBLG268AGGT2022/10/15812022/10/11813、MiscellaneousAssaysLeadcompoundsandcompoundsofinterestforleadoptimizationareroutinelytestedforcytotoxicity,inhibitionofcytochromeP450isoenzymes(CYPs),compoundpermeabilityinCaco-2cells,andspecificityinotherrelatedassays.Profilingofthecompoundsatthetimeoftheleadoptimizationisveryhelpfulforselectingcompoundstoinvivostudies.2022/10/15823、MiscellaneousAssaysLeadcom1)CellproliferationandcytotoxicityassaysTheeffectofcompoundsonthecellisgenerallyassessedwithnonspecificcytotoxicityassays.
CellviabilitytestCellMTT(tetrazolium)LivingcellsreduceMTTtoahighlycoloredformazensaltandcanbereadinaplatereaderasanendpointreading.MTT-relativelyinsoluble(MTS/XTT)AlamarBlueassays2022/10/15831)Cellproliferationandcyto2)CYPsLeadOptimizationstudiesADME/PKPromoteEarlyLeadsToCompoundsAbsorptionDistributionMetabolismExcretionPharmacokinetics2022/10/15842)CYPsLeadADME/PKPromoteEarl3)ChipTechnologiesMicrofabricationandmicrofluidies-basedchiptechnologyisemergingandmayreplaceHTSwithfurtherminiturizationMicrochiptechnologyhasbecomeapowerfultechnologyandiswidelyusedinDNAanalysis.2022/10/15853)ChipTechnologiesMicrofabriDNAchiptechnologyWithinthedepartmentofMolecularGenetics,DNAchiptechnologyisacoreactivity.Thistechnology,whichisalsosynonymouswithDNAmicro-arrayanalysis,aimsattakingaglobalviewofgeneactivities,thusenablingtheresearchertosimultaneouslyfollowthe
expressionlevelsofthousandsofgenesinasingleexperiment.Thepurposeofthisistogainmolecularunderstandingofthebiologicalactionofdrugcandidatemoleculestohelpselectanddevelopoptimaldrugs.Furthermore,throughglobalgeneexpressionanalysisindiseasemodels/treatmentsystems,itisalsopossibletoidentifynoveltargetsforfuturedrugdevelopment.Averyimportantaspectof
DNAchiptechnologyistheabilitytoidentifybiomarkersthatcanbeusedtoreadilymonitordrugefficaciesa
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