Medicinal Chemistry Approaches to Personalized Medicine

StructuresDeveloping Superior Quadruplex-Binding LigandsConclusionsIDENTIFYING ACTIONABLE TARGETS IN CANCER PATIENSIntroduction and BackgroundOverview of Genomic Sequencing and Its Impact on the Identification of Actionable MutationsActionable Targets by Clinical Molecular Profiling: The OICR/PMH ExperienceSome Exeriences of Other Clinical Oncology Molecular Profiling StudiesIdentifying Secondary and Novel Mutations through Molecular ProfilingUnderstanding and Targeting Resistance Mutations: A Challenge and an Opportunity for NGSConcluding Remarks and Future PerspectivesDNA DAMAGE REPAIR PATHWAYS AND SYNTHETIC LETHALITYIntroductionDNA Damage ResponseSynthetic LethalityLead Case Study: PARP InhibitorsAdditional Case StudiesScreening for Synthetic LethalityContextual Synthetic Lethality ScreeningCancer Stem CellsConclusions and Future DirectionsAMYLOID CHEMICAL PROBES AND THERANOSTICS: STEPS TOWARD PERSONALIZED MEDICINE IN NEURODEGENERATIVE DISEASESIntroductionAmyloid Plaques as the Biomarker in ADDetecting Amyloid Plaques in Patiens: From Alois Alzheimer to Amyvid and BeyondSame Causes, Same Imaging Agents?Theranosticcs in ADConclusions and PerspectivesFROM HUMAN GENETICS TO DRUG CANDIDATES: AN INDUSTRIAL PERSPECTIVE ON LRRK2 INHIBITION AS A TREATMENT FOR PARKINSON'S DISEASEIntroductionBiochemical Studies of LRRK2 FunctionCellular Studies in LRRK2 FunctionAnimal Models of LRRK2 FunctionClinical Studies of LRRK2-Associated PD and Future ProspectsSmall-Molecule Inhibitors of LRRK2Structural Models of the LRRK2 Kinase DomainStrategies Used to Identify LRRK2 Kinase Inhibitors (Overview)ConclusionsTHERAPEUTIC POTENTIAL OF KINASES IN ASTHMAIntroductionMitogen-Activated Protein KinasesNonreceptor Protein Tyrosine KinasesReceptor Tyrosine KinasesPhosphatidylinositol-3 KinasesAGC KinasesIkB KinaseOther KinasesConclusions: Future DirectionsDEVELOPING TARGETED PET TRACERS IN THE ERA OF PERSONALIZED MEDICINEImaging and Pharmacodynamics Biomarkers in Drug DevelopmentGeneral Considerations for Development of 11C- and 18F-labeled PET TracersRadiolabeling Compounds with 11CRadiolabeling Compounds wiht 18FPET Imaging in the Clinic, Research, and Drug DevelopmentPET Tracer Kinetic Modeling for Quantification of Tracer UptakeConcluding RemarksMEDICINAL CHEMISTRY IN THE CONTEXT OF THE HUMAN GENOMEIntroductionDrugs Targeting KinasesDrugs Targeting PhosphatasesIn silico-Based Lead Discovery in the GPCR FamilyTargeting Epigenetic Regulation: Histone DemethylasesTargeting Epigenetic Regulation: Histone DeacetylasesA Family-Wide Approach to Poly(ADP-Ribose) PolymerasesFuture Drug Target Superfamilies: Ubiquitination and DeubiquitinationSummary and OutlookIndex