Discovery to IND Filing, 2nd Edition

CHAPTER 1: INTRODUCTION
The Process

CHAPTER 2: DRUG DISCOVERY
Introduction
Biology of the Disease
Selecting a Drug Target
Target Types
DNA
RNA
Protein
How Many Targets?
The Druggable Genome
Implications for Drug Discovery

CHAPTER 3: DRUG TARGET IDENTIFICATION AND VALIDATION
Introduction
The Human Genome Project
The Major Findings
Implications for Drug Discovery
The Promise of Genomics
Genomics and Drug Discovery
Unresolved Issues
Target Identification
Role of Functional Genomics
Knockouts
Antisense
RNA Interference
Transgenics
Limitations of Gene-modified Animal Models
DNA Microarrays
Bioinformatics Techniques
Identification of Drug targets: Tools and Techniques
Molecular Biology Techniques
DNA-Related Techniques
RNA-Related Techniques
Protein Related Techniques
Proteomics
Drug Target Validation
DTV Techniques

CHAPTER 4: SCREENING THE DRUG TARGET
Discovery Screens
Small Molecule Screening Libraries
Combinatorial Chemistry
HTS Assay
HTS Phenotypic Outcomes
The Impact of HTS

CHAPTER 5: DEVELOPING LEADS FROM HITS
The Importance of Druggability
Predicting Druggability
Artificial Intelligence Screening
Lead Discovery
Lead Optimization
What is an Optimized Lead Molecule
Why Preclinical Candidates are Discontinued: Starting Points for Lead Optimization
Pharmacology and Toxicology
Scalability of Synthesis
Regulatory Issues in Lead Optimization
Strategy Precedes Paperwork
The Implicit "Acknowledged Disorder" Criterion
Optimizing Lead Compounds with a Regulatory View to Synthesis
The "Strategy of the Backups"
Lead Optimization and Development

CHAPTER 6: DRUG DEVELOPMENT PROCESS: FROM LEAD TO IND FILING
Preclinical Development
Post-Discovery Process
Chemistry and Synthesis of Drug Molecules
Drug Development Phase
Pharmacology or In Vitro and Animal Model Efficacy
Route of Administration
Defining the Appropriate Dose
Defining the Right Animal Models
In vivo Dosage
Drug Developability Stage
Preliminary Formulation Evaluation
Toxicity
Drug Metabolism
Formulation Development
Bioanalytical Chemistry Method Validation
IND-Directed Toxicology Studies
Pharmacokinetics and Drug Metabolism
Mechanism of Action Studies
Other Required IND Application Studies
Manufacturing Program
Quality Control Process
Clinical
Pharmacokinetics and Drug Metabolism
Mechanism of Action
Phase 1: Safety and Tolerance Study
Phase 2: Efficacy Studies
Phase 3: Definitive Safety and Efficacy Studies
Phase 4: Studies
Filing an IND Application

CHAPTER 7: SUMMARY AND CONCLUSIONS
Recent Trends

CHAPTER 8: ADDITIONAL READING

CHAPTER 9: APPENDICES
Appendix 1: Stepwise Guide to Antibody Development for Therapeutics
Appendix 2: Stepwise Guide to Small Molecule Development for Therapeutics