Table of Contents
About the Editors xv
Acknowledgments xvii
Contributors xix
Introduction 1 Michael J. Barratt and Donald E. Frail
References 5
Part I. Drug Repositioning: Business Case, Strategies, and Operational Consideration 7
1. Drug Repositioning: The Business Case and Current Strategies to Repurpose Shelved Candidates and Marketed Drugs 9 John Arrowsmith and Richard Harrison
2. Opportunities and Challenges Associated with Developing Additional Indication for Clinical Development Candidates and Marketed Drugs 33 Donald E. Frail and Michael J. Barratt
3. Clinical and Operational Considerations in Repositioning Marketed Drugs and Drug Candidates 53 Damian O’Connell, David J. Sequeira, and Maria L. Miller
4. Regulatory Considerations and Strategies for Drug Repositioning 65 Ken Phelps
Part II. Application of Technology Platforms to Uncover New Indications and Repurpose Existing Drugs 89
5. Computational and Bioinformatic Strategies for Drug Repositioning Drugs 91 Richard Mazzarella and Craig Webb
6. Mining Scientific and Clinical Databases to Identify Novel Uses for Existing Drugs 137 Christos Andronis, Anuj Sharma, Spyros Deftereos, Vassilis Virvilis, Ourania Konstanti, Andreas Persidis, and Aris Persidis
7. Predicting the Polypharmacology of Drugs: Identifying New Uses through Chemoinformatics, Structural Informatics, and Molecular Modeling-Based Approaches 163 Li Xie, Sarah L. Kinnings, Lei Xie, and Philip E. Bourne
8. Systematic Phenotypic Screening for Novel Synergistic Combinations: A New Paradigm for Repositioning Existing Drugs 207 Margaret S. Lee
9. Phenotypic In Vivo Screening to Identify New, Unpredicted Indications for Existing Drugs and Drug Candidates 253 Michael S. Saporito, Christopher A. Lipinski, and Andrew G. Reaume
10. Old Drugs Yield New Discoveries: Examples from the Prodrug , Chiral Switch, and Site-Selective Deuteration Strategies 291 Adam J. Morgan, Bhaumik A. Pandya, Craig E. Masse, and Scott L. Harbeson
Part III. Academic and Nonprofit Initiatives and the Role of Alliances in the Drug Repostioning Industry 345
11. Repurposing Drugs for Tropical Disease: Case Studies and Open-Source Screening Initiatives 347 Curtis R. Chong
12. Drug Repositioning Efforts by Nonprofit Foundations 389
13. Business Development Strategies in the Repositioning Industry 433 Aris Persidis and Elizabeth T. Stark
14. A Case Study in Drug Repositioning: Sosei 445 Akinori Mochizuki and Makiko Aoyama
Appendix Additional Drug Repositioning Resources and Links 457 Mark A. Mitchell and Michael J. Barratt
Index 469