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Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease

Book Description

An authoritative look at the application of chemical biology in drug discovery and development

Based on the award-winning Wiley Encyclopedia of Chemical Biology published in 2008, this book explores the role of chemical biology in drug discovery and development. The first part of the book reviews key principles and techniques used in the design and evaluation of drug candidates. The second part elucidates biological mechanisms of certain diseases, illuminating approaches to investigate and target these diseases.

Comprising carefully selected reprints from the Encyclopedia as well as new contributions from leading scholars in the field, this book provides researchers in academia and industry with important information to aid in the development of novel agents to treat disease. Self-contained articles cover a variety of essential topics, including:

  • The design, development, and optimization of drug candidates

  • The pharmacokinetics and properties of drugs

  • Drug transport and delivery

  • Natural products and natural product models as pharmaceuticals

  • Biological mechanisms underlying health and disease

  • Treatment strategies for a range of diseases, from HIV to schizophrenia

Chemical Biology is a top-notch guide and reference for anyone working in the areas of drug discovery and development, including researchers in chemical biology and other fields such as biochemistry, medicine, and pharmaceutical sciences.

Table of Contents

  1. Cover
  2. Copyright
  3. Title Page
  4. Preface
  5. Contributors
  6. Part I: Drug Discovery and Development
    1. Chapter 1: The Role of Chemical Biology in Drug Discovery
      1. 1.1 Introduction
      2. 1.2 Target Identification and Validation
      3. 1.3 Reagent and Assay Development
      4. 1.4 Lead Discovery
      5. 1.5 Hit to Lead/Probe
      6. 1.6 Lead Optimization
      7. 1.7 Conclusions
    2. Chapter 2: Computational Approaches to Drug Discovery and Development
      1. 2.1 Target Identification
      2. 2.2 Lead Discovery
      3. 2.3 ADME/T Optimization
      4. 2.4 The Future
    3. Chapter 3: Design and Selection of Small Molecule Inhibitors
      1. 3.1 Virtual Screening in Selecting Small Molecule Inhibitors
      2. 3.2 Receptor-Based VLS
      3. 3.3 Ligand-Based Virtual Screening (2-D Similarity Search, 3-D Pharmacophore Search)
      4. 3.4 Design of Small Molecule Inhibitors
      5. 3.5 Scaffolds and Fragments-Based Lead Design
      6. 3.6 Hybrid Design Based on Known Inhibitors
      7. 3.7 De Novo Design
      8. 3.8 Hit and Lead Optimization
      9. 3.9 Structure Based
      10. 3.10 Qsar Based
      11. 3.11 Design of Selective Small Molecule Inhibitors
      12. 3.12 Targeting the Differences in the Binding Pocket
      13. 3.13 Engineering Selectivity Using Chemical Genetics
      14. 3.14 Summary
    4. Chapter 4: Lead Optimization in Drug Discovery
      1. 4.1 Advances in High-Throughput Screening Technologies
      2. 4.2 Solution-Phase Parallel Synthesis for Lead Optimization
      3. 4.3 Expedited Drug Metabolism and Pharmacokinetics
      4. 4.4 Expedited, “Closed-Loop” Work Flow for Lead Optimization
    5. Chapter 5: Pharmacokinetics of Drug Candidates
      1. 5.1 Clinical Pharmacokinetics
      2. 5.2 Role of PK in the Drug Discovery and Development Process
      3. 5.3 Summary
    6. Chapter 6: ADME Properties of Drugs
      1. 6.1 Solubility
      2. 6.2 Permeability
      3. 6.3 Stability
      4. 6.4 Cytochrome P450 Inhibition
      5. 6.5 Other ADME/TOX Properties
    7. Chapter 7: Drug Transport in Living Systems
      1. 7.1 Multidrug Transporters (MDTs)
      2. 7.2 Insights Into Structures of MDTs
      3. 7.3 Substrate Recognition: Multiple Drug Binding Proteins
      4. 7.4 Transport Mechanisms of MDTs
      5. 7.5 Physiologic Roles and Natural Substrates
      6. Acknowledgment
    8. Chapter 8: Blood-Brain Barrier: Considerations in Drug Development and Delivery
      1. 8.1 Cellular Physiology of the Blood-Brain Barrier
      2. 8.2 Drug Delivery to the Brain
      3. 8.3 Strategies to Improve CNS Drug Delivery
      4. Acknowledgments
    9. Chapter 9: Pharmacokinetic Considerations: Methods and Systems of Controlled Drug Delivery
      1. 9.1 General Introduction of Pharmacokinetics/ Pharmacodynamics
      2. 9.2 Pharmacokinetic/Pharmaceutical Dosage Form/Pharmacodynamic Considerations in the Design of A Controlled Drug Delivery System
      3. 9.3 Methods and Systems of Controlled Drug Delivery
      4. 9.4 Summary
    10. Chapter 10: Pharmaceuticals: Natural Products and Natural Product Models
      1. 10.1 Introduction
      2. 10.2 Antibacterial Agents
      3. 10.3 Antifungal Agents
      4. 10.4 Antimalarials
      5. 10.5 Antivirals
      6. 10.6 Antipain Agents
      7. 10.7 Antiobesity
      8. 10.8 Alzheimer's Agents
      9. 10.9 Antineoplastic Agents
      10. 10.10 Immunosuppressant Agents
      11. 10.11 Cardiovascular Agents
      12. 10.12 Antiparasitic Agents
      13. 10.13 Pharmaceutical Models
  7. Part II: Chemical Biology to Understand And Target Disease
    1. Chapter 11: The Role of Chemical Biology in Understanding and Treating Disease—Are Small Molecule “Correctors” the Way of the Future?
      1. 11.1 The Potential for Small-Molecule Correctors
    2. Chapter 12: Anxiety Disorders
      1. 12.1 Neuroticism and Anxiety
      2. 12.2 Genes, Their Protein Products, and Associated Biological Pathways Implicated in Anxiety and Anxiety-Like Behavior
      3. 12.3 Environmental Factors and Related Biological Pathways Involved in Anxiety
      4. 12.4 Interaction Between Genetic and Environmental Factors
      5. 12.5 Convergence of Anxiety-Related Pathways and Mechanisms
    3. Chapter 13: Chronic Obstructive Pulmonary Disease (COPD)
      1. 13.1 COPD as an Inflammatory Disease
      2. 13.2 Inflammatory Cells
      3. 13.3 T-Lymphocytes
      4. 13.4 Mediators of Inflammation
      5. 13.5 Conclusions
    4. Chapter 14: Depression
      1. 14.1 Introduction
      2. 14.2 Biogenic Amines
      3. 14.3 Classes of Antidepressants
      4. 14.4 Beyond Biogenic Amines
      5. 14.5 Other Antidepressant Approaches and Targets
      6. 14.6 Concluding Remarks
      7. Acknowledgments
    5. Chapter 15: Osteoarthritis
      1. 15.1 Biological and Biophysical Background of Osteoarthritis
      2. 15.2 Biochemistry and Molecular Mechanism Involved in Osteoarthritis
      3. 15.3 Tools and Methods for Studying Osteoarthritis
      4. 15.4 Therapeutic Management of Osteoarthritis
    6. Chapter 16: Human Immunodeficiency Virus (HIV)
      1. 16.1 Introduction
      2. 16.2 The Mechanism of Viral Infection
      3. 16.3 Conclusion
    7. Chapter 17: Allergy and Asthma
      1. 17.1 Biological Background
      2. 17.2 Small Molecules in Asthma
      3. 17.3 Targeting Inflammatory Cell Accumulation
      4. 17.4 Immunotherapy
    8. Chapter 18: Schizophrenia
      1. 18.1 Neurobiology (Neurochemistry) of Schizophrenia
      2. 18.2 Antipsychotics
      3. 18.3 Behavioral Phenotype
      4. 18.4 Antipsychotics Clinical Efficacy Profile
      5. 18.5 Adverse Effects Associated with Antipsychotic Treatments
      6. 18.6 Cholinergic Drugs (Positive Modulators of Muscarinic Receptors)
      7. 18.7 Gulatamatergic Drugs in the Treatment of Schizophrenia
    9. Chapter 19: Protein Misfolding and Disease
      1. 19.1 Introduction
      2. 19.2 Biological Background of Protein Misfolding Diseases
      3. 19.3 Biophysical Characterization of Fibrils and Molecular Mechanism of their Formation
      4. 19.4 Methods Used for Fibril Structure Determination and Aggregation Assays
    10. Chapter 20: Protein Trafficking Diseases
      1. 20.1 Quality Control in the ER
      2. 20.2 Protein Trafficking Diseases
      3. 20.3 Correctors of Protein Trafficking
      4. 20.4 Conclusions
      5. Acknowledgments
    11. Chapter 21: Metabolic Diseases
      1. 21.1 The Global Crisis in Obesity, Diabetes, and CV Risk
      2. 21.2 Underlying Mechanisms that Lead to Insulin Resistance and CVD
      3. 21.3 Current and Next Generation Therapeutics
    12. Chapter 22: Mitochondrial Medicine
      1. 22.1 Biological Background
      2. 22.2 The Chemistry of the OXPHOS System
      3. 22.3 Tools and Techniques to Study the OXPHOS System
      4. 22.4 Diagnostic Biochemical Analysis of the Mitochondrial Energy Generating System
    13. Chapter 23: Lysosomal Disorders
      1. 23.1 Endosomes and Lysosomes
      2. 23.2 Components of Endosomes and Lysosomes
      3. 23.3 Targeting of Protein Constituents to Lysosomes
      4. 23.4 Interaction of Endosomes and Lysosomes and the Site of Substrate Hydrolysis
      5. 23.5 Commonalities for Lysosomal Storage Disorders in Terms of Clinical Phenotype and Vesicular Pathology
      6. 23.6 Primary and Secondary Storage Materials
      7. 23.7 Impact of Storage on Vesicular Structure and Traffic
      8. 23.8 Treatment Strategies and Ability to Correct Residual Pathology
  8. Index