优秀学术报告PPT示例(Ari-Koskinen)

ChemistryinBiomedicineandDrugDiscoveryProfessorAriKoskinenHelsinkiUniversityofTechnology11.03.2005AriKoskinenLaboratoryofOrganicChemistryNumberapprovedbyFDA,024,021,718,616,215,513,712,51189,48,27,66,55,84,$/No.NewChemicalEntitiesvs.R&DExpedinture$billions600,705040302010086878889909192939495969798990,600,500,400,300,200,100,00R&DSpending$billionsNewmolecularentitiesapprovedbyFDARatio:$/No.Note:Ethicalpharmaceuticalsonly.ExpendituresworldwidebyU.S.-ownedresearch-basedpharmaceuticalcompaniesC&ENJanuary17,2000,Food&DrugAdministration,PharmaceuticalResearch&ManufacturersofAmerica:PhRMAAnnualSurvey2000.AriKoskinenLaboratoryofOrganicChemistryNewDrugDevelopmentAriKoskinenLaboratoryofOrganicChemistryR&DByGeographicArea;2001AfricaAmericasEuropeAsia-PacificAustraliaMiddleEastOthersAriKoskinenLaboratoryofOrganicChemistryab$1.7bn(2003)perproductisspentonR&DStageSynthesis/extractionBiologicalscreening/pharmacologicaltestingToxicology/safetyDosageformulationClinicalevaluationProcessdevelopmentformanufacturing/qualitycontrolRegulatoryOther%ofspendinga11.016.06.09.634.59.63.89.4%ofemployeesb12.918.37.811.624.310.34.810.0CompanyfinancedR&DinUSbasedon1995figurestotalling$11.8bnUSscientificandprofessionalpersonneltotaling34,784employeesSource:PharmaceuticalResearch&ManufacturersofAmerica,IndustryProfile19972003data:C&EN2003,81(50),8.AriKoskinenLaboratoryofOrganicChemistryMarketExclusivityTimesDecreaseAriKoskinenLaboratoryofOrganicChemistryDevelopmentpipelineAriKoskinenLaboratoryofOrganicChemistryTop10TherapiesDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryTop10ProductsDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryMergersDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryOffPatentDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryPatentsexpiringDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryPromisingNewDrugsDecember6,2004Volume82,Number49pp.18-29AriKoskinenLaboratoryofOrganicChemistryDiversityofDrugStructuresBODFEHOOGNaturalProductsasDrugLeadsOMeMeOONHClHOOMeOMeA1MeOClOAOMeOHONO2MeOOCOMeMeOOOMeOHMeOMeOOOOHOHOHOGOOMeOOHOOOOOHOMeA2OHMeMeMeOHOOOHOHOOMeMeOMeEverninomicin13,384-1MeCallipeltosideAClinhibitsproliferationofKBandP388cellsprotectscellsinfectedwithHIVO16OHMeBr46OMe43OHOMe33OOHN29OO24OO1NO9O5HOOHAOOMeBOHMeCDHOHEOOHHHNIMeHHOMeOHFMePhorboxazoleAAzaspiracidcausativeagentfor1995humanpoisoningsbycontaminatedIrishmusselsMytilusedulisAriKoskinenLaboratoryofOrganicChemistryHHONOSOONNHONNHOHMeNHRCONNMeSNCNNHHOONOOChemicalStrategiesinDrugDevelopmentIsolationStructurebasedsynthesisHONRationalDrugDesignOOMeHOOOHDesignbasedonChemicalDiversityMeCO2HClNNNONOHMorphine-Lactams(antibiotics)MeOOMeNMeStrychnineBrsplitTagametProgesterone(anti-ulcer)MeOMeOOOOMeHQuinineValiumBr(tranquilizer)AriKoskinenLaboratoryofOrganicChemistryHighThroughputScreeningPlants(500000)Marinenaturalproducts(106)Invertebratenaturalproducts(109)CompoundlibrariesStructurebaseddesignRecombinantmethodsPeptidelibrariesPeptidomimeticlibrariesAriKoskinenLaboratoryofOrganicChemistryDrugDevelopmentParadigmsTraditionalApproachClinical/preclinicalObservationsDiseasemodelinvivoLEADinvivoStudiesonpathophysiologyRationalApproachinvitroDiseasegeneorinvivoValidatedtargetinvitroLEADdesignTransgenicanimalsAriKoskinenLaboratoryofOrganicChemistryDrugDevelopmentParadigmsTARGETIDENTIFICATIONGeneralcombinatoriallibrariesLEADGENERATIONBiasedcombinatoriallibrariesLEADOPTIMIZATIONStructuralchemistryDRUGCANDIDATEAriKoskinenLaboratoryofOrganicChemistryChemicalDiversityBasissetof20Units203LibraryEntities8000(e.g.naturalaminoacids)204160000205Units3200000LibraryEntitiesThenumberofdifferentchemicalentities,N=bx,wherex=thenumberofsteps,andb=numberofdifferentbuildingblocks.Basissetof100(e.g.carbohydrates)100310041005Units100031Million100Million10BillionLibraryEntities1BillionTheproblemofcombinatorialsynthesisisnotthatofmakingcompounds,butthatoffindingwaystoselectandidentifythecompounds:Onemustbeabletoextracttheinformationmadeavailablebylibraryscreening.Basissetof1000(e.g.syntheticbuildingblocks)10004100051Trillion1QuadrillionAriKoskinenLaboratoryofOrganicChemistryCombinatorialChemistrysolid-phaseorganicchemistry(SPOC)combinatorialsynthesisstructureelucidationbasedondeconvolutionandtaggingstructure-diversityautomationReviews:SpecialIssue:Acc.Chem.Res.1996,29,#3(March).Hermkens,P.H.H.;Ottenheijm,H.C.J.;Rees,D.Tetrahedron1996,52,4527-4554.Früchtel,J.S.;Jung,G.Angew.Chem.,Int.Ed.Engl.1996,35,17-42.Lowe,G.Chem.Soc.Rev.1995,24,309.Ellman,J.Chemtracts:OrganicChemistry1995,8,1-4.Pirrung,M.C.Chemtracts:OrganicChemistry1995,8,5-12.Czarnik,A.W.Chemtracts:OrganicChemistry1995,8,13-18.Mitscher,L.A.Chemtracts:OrganicChemistry1995,8,19-25.Dolle,R.E.;Nelson,K.H.J.Combinator.Chem.1999,1,235-282.AriKoskinenLaboratoryofOrganicChemistry1987198919911993199519971985CombinatorialChemistryPublicationsCombinatorialChemistry140012001000#800600400200PatentsPublications0Yea