Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs

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