Foreword1. Drug Discovery and Development: An Overview of Modern Methods and PrinciplesDrug Discovery and Development from 20,000 FeetTarget Selection: The First Step ForwardHit Identification: Finding a Starting PointIdentify a Clinical Candidate: Juggling the PropertiesQuestionsReferences2. The Drug Discovery Process: From Ancient Times to the Present DayThe Age of Botanicals: Preindustrial Drug DiscoveryPaul Ehrlich: The Father of Modern Drug DiscoveryMilestones in Drug Discovery Milestones in Animal Models: Breeding a Better Model Milestones in Molecular Science X-ray Crystallography Molecular Modeling and Computational Chemistry High Throughput Technology: Chemical Synthesis and Screening Science Milestones in Biotechnology Recombinant DNA and Transfection Technology Polymerase Chain Reaction (PCR) Technology Monoclonal Antibody and Hybridoma TechnologyThe Rise of Biologics and Macromolecular TherapeuticsSocietal and Governmental Impacts The Pure Food and Drug Act of 1906 The Elixir of Sulfanilamide Disaster of 1937 The Thalidomide StoryRegulatory Milestones Durham-Humphrey Amendment of 1951 Kefauver-Harris Amendment of 1962 Hatch-Waxman Act of 1984 Biologics Price Competition and Innovation Act of 2009Future Developments in Drug DiscoveryQuestionsReferences3. Classical Targets in Drug DiscoveryProtein StructureEnzymesInhibition of EnzymesG-Protein-Coupled Receptors (GPCRs) G-Protein-Dependent Signaling pathways cAMP Signaling IP3 Signaling Modulating GPCR ActivityIon Channels Gating Mechanisms Ligand-Gated Channels Voltage-Gated Channels Other Gating MechanismsMembrane Transport Proteins (Transporters)Emerging TargetsQuestionsReferences4. In Vitro Screening SystemsThe Language of Screening: Basic Terms Concentration Response Curves and IC50s Dissociation Constants (Kd) and Inhibition Constants (Ki) Efficacy versus Binding: EC50s Agonist, Partial Agonist, Antagonist, Allosteric Modulators, and Inverse Agonists Agonists and Partial Agonists Antagonists Basal Activity and Inverse Agonists Allosteric Modulation Receptor ReserveStreptavidin and BiotinBiochemical versus Cellular AssaysAssay Systems and Methods of DetectionRadioligand Systems Scintillation Proximity Assay (SPA)Enzyme-Linked Immunosorbent Assay (ELISA)Fluorescence-Based Assay Systems Fluorescence Polarization (FP) Fluorescence Resonance Energy Transfer (FRET) Time-Resolved Fluorescence Resonance Energy Transfer (TRFRET) Amplified Luminescent Proximity Homogeneous Assay (AlphaScreenT) Fluorescent Detection of Calcium FluxReporter Gene Assays Chloramphenicol Acetyltransferase (CAT) ?-Lactamase Reporter Assays Luciferase Reporter AssaysKinetic Fluorescent Measurement SystemsLabel-Free Assay Systems Cellular Dielectric Spectroscopy Optical Biosensors Surface Plasmon Resonance TechnologyElectrophysiological Patch ClampGeneral Consideration for All Screening MethodsQuestionsReferences5. Medicinal ChemistryStructure-Activity Relationships and Structure-Property RelationshipsThe Role of ChiralityPush and Pull in Structure-Activity RelationshipsQuantitative Structure-Activity RelationshipsThe PharmacophoreDeveloping an SAR Data SetThe Structure-Activity Relationship CycleBioisosterismStructure-Activity Relationship, Selectivity and Physicochemical Properties"Druglike” GuidelinesQuestionsReferences6. In vitro ADME and In vivo PharmacokineticsAbsorption Solubility PermeabilityDistribution Permeability Transporters Plasma Protein BindingElimination Pathways Metabolism ExcretionIn vitro ADME Screening MethodsIn Vivo Pharmacokinetics Volume of Distribution Clearance Half-life BioavailabilitySpecies selectionQuestionsRefere