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

Michael Barratt is an independent consultant and previously?Senior Director and Technology Platform Leader at Pfizer's Global Indications Discovery Research Unit. He has?over 15?years of experience in preclinical drug discovery research and leadership. Donald Frail is an independent consultant and previously?Vice President of Pfizer Global Research and Development and Head of Pfizer's Global Indications Discovery Research Unit. He has over 20 years of industrial research and management experience in preclinical drug discovery and early clinical research.

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