学习抗癌药研究ppt课件.ppt
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1、Anti-cancerDrugDiscoveryandDevelopment Outline vAnti-cancerdrugdiscoveryprocessvTheapproachtoanti-cancerdrugdiscoveryvIdentificationandvalidationoftargetvComputeraideddrugdesignvSmallMolecularsscreeningthroughHTSvMetabolicandPhysicochemicalProfilingofdrugvCancerresistanceAnti-cancerdrugdiscoveryproc
2、essvModernmolecularbiologyandgenomics/proteomicstoidentifyandvalidatenewtherapeutictargetsvCombinatorialchemistryfortheefficientgenerationofstructuraldiversityandforrapidproductionofalibraryofstructuralanaloguesbasedonanidentifiedleadcompoundandoptimization,enhancedstructuralbiologyandmolecularmodel
3、ingtechniquesforrationaldrugdesignvRobotichigh-throughputscreeningagainststructurallydiversechemicallibrariestodiscoverleaddrugsvHigh-throughputpharmacokineticsassays,theuseofsurrogateendpointstomonitorpharmacodynamicsthroughoutthediscoveryanddevelopmentprocess,particularlyinvolvinggenomics(e.g.,nuc
4、leicacidmicroassays)andproteomicsThe approach to anti-cancer drug discoveryvcell-basedscreeningvTargetingthespecificmolecularlesionsCell-basedscreening1.cell-basedcytotoxicityassays:randomhigh-throughputscreeningofsyntheticcompoundsandnaturalproducts,basedonanti-proliferativeeffects2.syntheticcompou
5、ndsandnaturalproductsbelongtoDNA-damaging agents with a low therapeutic index,Nottargetthemolecularlesionsresponsibleformalignanttransformation NCI: highlychemo-sensitiveP388leukemiacelllineTarget-basedscreeningforanti-cancerdrugdiscoveryvIdentification and validation of targetvEmerging targetsvDrug
6、 design and HTSIdentificationandvalidationoftargetvGenomicsanalytictechnology:microarrayanalysis,high-throughtRNAi,Ambion,Inc. CenixBioSciencevProteomicsanalytictechnology:affinitychromatographyandmassspectrometry vX-omicsanalytictechnologyEpigenomics(DNAmethylationandhistonedeacelylation),Cytomics,
7、Metabolomics,Interatomics,BioinformomicsEmerging targetsvOncogenesandapoptosis-inhibitinggenes,mainlyencodingproteinsthatarecomponentsofsignaltransductionpathwaysthatregulateproliferation,differentiation,invasion/metastasis,angiogenesisand/ortumorapoptosisorcelldeathvTargetsfacilitatingtumor-microen
8、vironmentinteractionsandmetastasisvtheMoffittCancerCenterDrugDiscoveryProgramattheUniversityofSouthFloridavUniversityofIllinois:FoxM1InhibitorsareAnticancerDrugsthatInduceCellDeathvtargetingWntsignalingvmiRNAs,vHedgehogsignalingvtheNotchpathwayvmetabolicpathwaysvtheimmunesystemvspecificinflammatorym
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