Basic principles of drug discovery and development / Benjamin E. Blass.

Includes bibliographical references and index.

Note continued: Nitrofurantoin: A Surprisingly Successful Drug -- Seldane� (Terfenadine) versus Allegra� (Fexofenadine): Metabolism Matters: Safety -- Claritin� (Loratadine) versus Clarinex� (Desloratadine): Metabolism Matters: Pharmacokinetics -- MPTP: Parkinson\'s Disease in a Bottle -- Bupropion and Methylphenidate: Improving Performance via Formulation Changes -- Selective Inhibition of Cyclooxygenase-2: The Impact of an Inadequate Written Description -- Questions -- References.

Machine generated contents note: 1.Drug Discovery and Development: An Overview of Modern Methods and Principles -- Drug Discovery and Development from 20,000 Feet -- Target Selection: The First Step Forward -- Hit Identification: Finding a Starting Point -- Identify a Clinical Candidate: Juggling the Properties -- Questions -- References -- 2.The Drug Discovery Process: From Ancient Times to the Present Day -- The Age of Botanicals: Preindustrial Drug Discovery -- Paul Ehrlich: The Father of Modern Drug Discovery -- Milestones in Drug Discovery -- Milestones in Animal Models: Breeding a Better Model -- The Wistar Rat -- Immunocompromised Mice -- Transgenic Animal Models -- Knockout Animal Models -- 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 --

Note continued: Polymerase Chain Reaction (PCR) Technology -- Monoclonal Antibody and Hybridoma Technology -- The Rise of Biologics and Macromolecular Therapeutics -- Societal and Governmental Impacts -- The Pure Food and Drug Act of 1906 -- The Elixir of Sulfanilamide Disaster of 1937 -- The Thalidomide Story -- Regulatory Milestones -- Durham -- Humphrey Amendment of 1951 -- Kefauver -- Harris Amendment of 1962 -- Hatch -- Waxman Act of 1984 -- Biologics Price Competition and Innovation Act of 2009 -- Future Developments in Drug Discovery -- Questions -- References -- 3.Classical Targets in Drug Discovery -- Protein Structure -- Enzymes -- Inhibition of Enzymes -- G-Protein-Coupled Receptors (GPCRs) -- G-Protein-Dependent Signaling Pathways -- cAMP Signaling -- IP3 Signaling -- Modulating GPCR Activity -- Ion Channels -- Gating Mechanisms -- Ligand-Gated Channels -- Voltage-Gated Channels -- Other Gating Mechanisms -- Membrane Transport Proteins (Transporters) --

Note continued: Emerging Targets -- Questions -- References -- 4.In vitro Screening Systems -- The 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 Reserve -- Streptavidin and Biotin -- Biochemical versus Cellular Assays -- Assay Systems and Methods of Detection -- Radioligand Assay 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 (AlphaScreen[�]) --

Note continued: Fluorescent Detection of Calcium Flux -- Reporter Gene Assays -- Chloramphenicol Acetyltransferase (CAT) -- �-Lactamase Reporter Assays -- Luciferase Reporter Assays -- Kinetic Fluorescent Measurement Systems -- Label-Free Assay Systems -- Cellular Dielectric Spectroscopy -- Optical Biosensors -- Surface Plasmon Resonance Technology -- Electrophysiological Patch Clamp -- General Consideration for All Screening Methods -- Questions -- References -- 5.Medicinal Chemistry -- Structure -- Activity Relationships and Structure -- Property Relationships -- The Role of Chirality -- Push and Pull in Structure -- Activity Relationships -- Quantitative Structure -- Activity Relationships -- The Pharmacophore -- Developing an SAR Data Set -- The Structure -- Activity Relationship Cycle -- Bioisosterism -- Structure -- Activity Relationship, Selectivity and Physicochemical Properties -- Druglike Guidelines -- Questions -- References --

Note continued: 6.In vitro ADME and In vivo Pharmacokinetics -- Absorption -- Solubility -- Permeability -- Distribution -- Permeability -- Transporters -- Plasma Protein Binding -- Elimination Pathways -- Metabolism -- Excretion -- In vitro ADME Screening Methods -- In vivo Pharmacokinetics -- Volume of Distribution -- Clearance -- Half-life -- Bioavailability -- Species Selection -- Questions -- References -- 7.Animal Models of Disease States -- Sources of Animal Models -- Validity of Animal Models -- Species Selection -- Number of Animals -- Exemplary Animal Models by Disease Category -- Animal Models in Neuroscience -- The Forced Swimming Test: A Model of Depression -- The Elevated Plus Maze: A Measure of Anxiety -- The Novel Object Recognition Test: A Model of Memory and Cognition -- Contextual Fear Conditioning Model: A Model of Contextual Learning -- The Morris Water Maze: A Model of Spatial Learning and Memory -- Animal Models of Neurodegeneration --

Note continued: The SOD1-G93A Mouse of Amyotrophic Lateral Sclerosis -- The MPTP Model of Parkinson\'s Disease -- Animal Models of Cardiovascular Disease -- Models of Hypertension -- Models of Hyperlipidemia and High Cholesterol -- Models of Atrial Fibrillation -- Models of Heart Failure -- Animal Models of Infectious Disease -- Murine Thigh Infection Model -- Murine Model of Systemic Infection -- The Mouse Model of Influenza Virus Infection -- Limitations of Animal Models of Infection -- Animal Models of Oncology -- Mouse Xenograft Tumor Model -- Mouse Allograft Tumor Model -- Genetically Engineered Mouse Models of Cancer -- Questions -- References -- 8.Safety and Toxicology -- Sources of Toxicity -- Acute versus Chronic Toxicity -- Cytotoxicity -- Carcinogenicity, Genotoxicity, and Mutagenicity -- Drug-Drug Interactions -- Cardiovascular Safety and Toxicology Studies -- Central Nervous System Safety and Toxicology Studies -- Immune System Mediated Safety Issues --

Note continued: Teratogenicity -- In vivo Toxicity and Safety Studies -- Questions -- References -- 9.Basics of Clinical Trials -- Before the Clinic -- Drug Supply -- Delivery Methods -- Formulation -- Investigational New Drug Application -- Phase I Clinical Trials -- Phase II Clinical Trials -- Phase III Clinical Trials -- Phase IV Clinical Trials -- Adaptive Clinical Trial Design -- Questions -- References -- 10.Translational Medicine and Biomarkers -- Definition of a Biomarker and Their Classification -- Characteristics and Impact of Biomarkers -- Biomarkers versus Surrogate End Points -- Imaging Technologies -- The Practical Application of Biomarkers -- DPP-IV Inhibitors (Januvia�) -- Physiological Measurements as Biomarkers: Orexin Antagonists -- FDG PET Imaging Agent -- The Neurokinin 1 (NK1) Receptor, Depression, and PET Imaging: The Aprepitant Story -- Questions -- References -- 11.Organizational Considerations and Trends in the Pharmaceutical Industry --

Note continued: Organizational Structures of Pharmaceutical Companies -- Business Divisions Interactions -- The Discovery Project Team Evolutionary Cycle -- The Business Climate -- Mergers and Acquisitions -- Contract Research Organizations -- Academic Drug Discovery -- Funding Issues -- Questions -- References -- 12.Intellectual Property and Patents in Drug Discovery -- Patentable Subject Matter -- Inherent Properties and Patentability -- Novelty and the Prior Art -- Obviousness and the Prior Art -- Inventorship -- Assignment and Ownership -- Classification of Patents and Patent Applications -- Impact of Overlapping Patents -- Patent Applications and Their Contents -- Contents of a Patent Application -- Questions -- References -- 13.Case Studies in Drug Discovery -- Tamiflu: From Mechanism of Action to Marketed Drug -- Histone Deacylase Inhibitors: Physicochemical Optimization via Structural Change -- HIV Protease Inhibitors: Chemically Complex Miracle Drugs --

'Basic Principles of Drug Discovery and Development' presents the multifaceted process of identifying a new drug in the modern era, providing comprehensive explanations of enabling technologies such as high throughput screening, structure based drug design, molecular modelling, pharmaceutical profiling, and translational medicine, all areas that have become critical steps in the successful development of marketable therapeutics.