Basic Principles of Drug Discovery and Development

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 modeling, pharmaceutical profiling, and translational medicine, all areas that have become critical steps in the successful development of marketable therapeutics.

The text introduces the fundamental principles of drug discovery and development, also discussing important drug targets by class, in vitro screening methods, medicinal chemistry strategies in drug design, principles in pharmacokinetics and pharmacodynamics, animal models of disease states, clinical trial basics, and selected business aspects of the drug discovery process. It is designed to enable new scientists to rapidly understand the key fundamentals of drug discovery, including pharmacokinetics, toxicology, and intellectual property."

• Provides a clear explanation of how the pharmaceutical industry works
• Explains the complete drug discovery process, from obtaining a lead, to testing the bioactivity, to producing the drug, and protecting the intellectual propertyIdeal for anyone interested in learning about the drug discovery process and those contemplating careers in the industry
• Explains the transition process from academia or other industries

upper undergraduates/graduate students interested in drug discovery research, chemistry, biology, pharmacology, biochemistry, toxicology, formulations, discovery/development of new therapeutic agents; pharmaceutical industry; FDA, public policy groups interested in influencing the pharmaceuticals industry; business analysts, entrepreneurs, venture capitalist interested in investing in the pharmaceuticals industry

• Dedication
• Foreword
• Chapter 1. Drug Discovery and Development: An Overview of Modern Methods and Principles
  • Drug Discovery and Development from 20,000 Feet (Figure 1.7)
  • Target Selection: The First Step Forward
  • Hit Identification: Finding a Starting Point
  • Identify a Clinical Candidate: Juggling the Properties
  • Questions
• Chapter 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
  • The Rise of Biologics and Macromolecular Therapeutics
  • Societal and Governmental Impacts
  • Regulatory Milestones
  • Future Developments in Drug Discovery
  • Questions
• Chapter 3. Classical Targets in Drug Discovery
  • Protein Structure
  • Enzymes
  • Inhibition of Enzymes
  • G-Protein-Coupled Receptors (GPCRs)
  • Ion Channels
  • Membrane Transport Proteins (Transporters)
  • Emerging Targets
  • Questions
• Chapter 4. In vitro Screening Systems
  • The Language of Screening: Basic Terms
  • Streptavidin and Biotin
  • Biochemical versus Cellular Assays
  • Assay Systems and Methods of Detection
  • Radioligand Assay Systems
  • Enzyme-Linked Immunosorbent Assay (ELISA)
  • Fluorescence-Based Assay Systems
  • Reporter Gene Assays
  • Kinetic Fluorescent Measurement Systems
  • Label-Free Assay Systems
  • Electrophysiological Patch Clamp
  • General Consideration for All Screening Methods
  • Questions
• Chapter 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
• Chapter 6. In vitro ADME and In vivo Pharmacokinetics
  • Absorption
  • Distribution
  • Elimination Pathways
  • In vitro ADME Screening Methods
  • In Vivo Pharmacokinetics
  • Species selection
  • Questions
• Chapter 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 of Infectious Disease
  • Animal Models of Oncology
  • Questions
• Chapter 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
  • Teratogenicity
  • In Vivo Toxicity and Safety Studies
  • Questions
• Chapter 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
• Chapter 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
  • Questions
• Chapter 11. Organizational Considerations and Trends in the Pharmaceutical Industry
  • 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
• Chapter 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
• Chapter 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
  • 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
• Answers to Questions in Textbook by Chapter
• Subject Index
• Drug Index