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

The how′s and why′s of successful drug repositioning

Drug repositioning, also known as drug reprofiling or repurposing, has become an increasingly important part of the drug development process. This book examines the business, technical, scientific, and operational challenges and opportunities that drug repositioning offers. Readers will learn how to perform the latest experimental and computational methods that support drug repositioning, and detailed case studies throughout the book demonstrate how these methods fit within the context of a comprehensive drug repositioning strategy.

Drug Repositioning is divided into three parts:

Part 1, Drug Repositioning: Business Case, Strategies, and Operational Considerations, examines the medical and commercial drivers underpinning the quest to reposition existing drugs, guiding readers through the key strategic, technical, operational, and regulatory decisions needed for successful drug repositioning programs.

Part 2, Application of Technology Platforms to Uncover New Indications and Repurpose Existing Drugs, sets forth computational–based strategies, tools, and databases that have been designed for repositioning studies, screening approaches, including combinations of existing drugs, and a look at the development of chemically modified analogs of approved agents.

Part 3, Academic and Non–Profit Initiatives & the Role of Alliances in the Drug Repositioning Industry, explores current investigations for repositioning drugs to treat rare and neglected diseases, which are frequently overlooked by for–profit pharmaceutical companies due to their lack of commercial return.

The book′s appendix provides valuable resources for drug repositioning researchers, including information on drug repositioning and reformulation companies, databases, government resources and organizations, regulatory agencies, and drug repositioning initiatives from academia and non–profits.

With this book as their guide, students and pharmaceutical researchers can learn how to use drug repositioning techniques to extend the lifespan and applications of existing drugs as well as maximize the return on investment in drug research and development.

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, andOperational Consideration 7

1. Drug Repositioning: The Business Case and Current Strategiesto Repurpose Shelved Candidates and Marketed Drugs 9
John Arrowsmith and Richard Harrison

 2. Opportunities and Challenges Associated with DevelopingAdditional Indication for Clinical Development Candidates andMarketed Drugs 33
Donald E. Frail and Michael J. Barratt

3. Clinical and Operational Considerations in RepositioningMarketed Drugs and Drug Candidates 53
Damian O Connell, David J. Sequeira, and Maria L.Miller

4. Regulatory Considerations and Strategies for DrugRepositioning 65
Ken Phelps

Part II. Application of Technology Platforms to Uncover NewIndications and Repurpose Existing Drugs 89

5. Computational and Bioinformatic Strategies for DrugRepositioning Drugs 91
Richard Mazzarella and Craig Webb

6. Mining Scientific and Clinical Databases to Identify NovelUses for Existing Drugs 137
Christos Andronis, Anuj Sharma, Spyros Deftereos, VassilisVirvilis, Ourania Konstanti, Andreas Persidis, and ArisPersidis

7. Predicting the Polypharmacology of Drugs: Identifying NewUses through Chemoinformatics, Structural Informatics, andMolecular Modeling–Based Approaches 163
Li Xie, Sarah L. Kinnings, Lei Xie, and Philip E. Bourne

8. Systematic Phenotypic Screening for Novel SynergisticCombinations: A New Paradigm for Repositioning Existing Drugs207
Margaret S. Lee

9. Phenotypic In Vivo Screening to Identify New,Unpredicted Indications for Existing Drugs and Drug Candidates253
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 ofAlliances in the Drug Repostioning Industry 345

11. Repurposing Drugs for Tropical Disease: Case Studies andOpen–Source Screening Initiatives 347
Curtis R. Chong

12. Drug Repositioning Efforts by Nonprofit Foundations 389

13. Business Development Strategies in the RepositioningIndustry 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 Links457
Mark A. Mitchell and Michael J. Barratt

Index 469

Overall, this book is so complete that it is a must readfor all the players in drug repositioning, not only researches or drug developers, but also business developmentspecialist, investors, venture capital firms, academia andregulators that need a compressive description that will satisfynovice and more experienced professionals.  (ChemMedChem, 1 March 2013)