Drug Repositioning (eBook)

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

"Overall, this book is so complete that it is a must read
for all the players in drug repositioning, not only
researches or drug developers, but also business development
specialist, investors, venture capital firms, academia and
regulators that need a compressive description that will satisfy
novice and more experienced professionals."
(ChemMedChem, 1 March 2013)