In particular, structure‐based drug design has had a profound impact on modern drug discovery. For example, physics‐based free‐energy perturbation could finally be used to realistically predict relative ligand‐binding potency after almost 30 years of effort. CryoEM technology, which was the subject of the 2017 Nobel Prize in Chemistry, has also shown an increasing impact on structure‐based drug design and enabled access to previously unobtainable protein structures. Artificial intelligence has also started to play an important role in drug discovery, although more time is needed to realize its full impact. These are very encouraging results; however, it still takes a long time to transform the initial basic discoveries from academic labs into a drug product. For example, a number of studies have shown that on average, it still takes more than 10 years and several billion dollars to develop and bring a new drug to market from the hit‐finding stage. Furthermore, the failure rate for clinical compounds remains unacceptably high at about 90% with some therapy areas suffering even higher rates. With these important advances and challenges in the drug discovery field, we feel that it is the right time to have a new edition of the book to showcase these new developments in driving the drug discovery process. In the first edition of the case study book, we mainly focused on marketed small molecule drugs and covered their discovery and development stories from initial biological rational to products on the market. In the new edition of the book, we not only cover the full stories of several marketed small molecule drugs but also include drug candidates with different modalities such as antibody drug conjugates, proteolysis targeting chimeras, and peptide drugs. The application of new technology such as DNA‐encoded library and positron emission tomography in drug discovery will also be covered in the book. Improving the drug discovery success rate continues to be a key factor that will weigh heavily on the success, and perhaps even the survival, of the pharmaceutical industry. How to more efficiently apply drug discovery principles and technologies to improve the success rate becomes a critical question. Knowledge gained from the successful discovery and launch of marketed drugs, and lessons learned from failed drug discovery stories can provide a very useful and important template for future drug design and discovery. We hope that the new edition of Case Studies in Modern Drug Discovery and Development (newly named as Contemporary Accounts in Drug Discovery and Development) can serve this purpose in addition to bringing educational value to the readers. Like the first edition, each chapter will have a detailed biological rational and background information, drug design principles, SAR development, ADMET considerations, and clinical studies, with modern drug discovery principles and technologies incorporated.
Like the first edition, this edition of Case Studies in Modern Drug Discovery and Development covers almost all aspects of the drug discovery process with detailed examples to showcase the science and technology; thus, it essentially will be suitable for all levels of scientists who are involved in drug discovery. The main targeted readers are medicinal chemists, and undergraduate and graduate students who are interested in drug discovery. Since it not only traces the drug discovery process from idea to marketed drug with a detailed explanation of the application of modern drug design principles and discovery technologies, but also showcases the importance of cross‐disciplinary applications of knowledge from different fields such as computer science and statistics, Contemporary Accounts in Drug Discovery and Development essentially will be beneficial to any scientist involved in the drug discovery process. It is also designed to be used as a textbook in a medicinal chemistry class. The book has 15 chapters and fits one full semester. With the comprehensive information included in each independent chapter, it is also suitable for professional seminars or courses that relate to drug design. Some of the drug discovery stories collected in this book are popular and life‐saving medications, so it will be of interest to the public who want to learn more about how these drugs are discovered.
Editing a scientific book is not an easy process; it took more than three years from the conception of the book, author recruiting, and chapter editing to the publication of the book. During this long process, there are many friends and colleagues who helped to make it possible. We would like to thank our editor, Jonathan Rose, for initiating the process, giving us the opportunity, and trusting us in editing Contemporary Accounts in Drug Discovery and Development. We also want to thank Wiley Managing Editor Dr. Andreas Sendtko for his role as a consistent point of contact both during the writing phase and right through to publication. His support has made the book‐editing process run very smoothly. We would also like to thank all the authors who dedicated their time to contribute the chapters and their respective companies for permission to publish their work. Without their unselfish contributions, especially during an unprecedentedly difficult period of the COVID‐19 pandemic, it is almost impossible to accomplish such a daunting job. We salute them for their time, effort, persistence, and dedication. We continue to believe that all the chapters will have a very important impact on future drug discovery programs and benefit future scientists of this field for generations to come. We would like to thank the reviewers of our book proposal for their valuable suggestions and critiques. We would like to thank Dr. Wen‐Lian Wu for his inputs/comments on the Alzheimer's disease chapter and Dr. Shuangping Shi for her expert comments on Appendix A. Xianhai is indebted to his wife Dr. Hongmei Li and his children Alexander and Angelina for their support and understanding. Bob would like to thank his wife Antoinette and his family for their encouragement and support over the years. Wayne is also grateful to the infinite support from his family.
The road to the discovery and development of life‐saving drugs is not and will never be easy and straightforward. With scientific advancements, technological innovations, close collaborations and knowledge sharing, and the lifetime dedication of pharmaceutical scientists and academic medical researchers, it is possible to improve the efficiency of drug discovery and development to deliver the therapies that will alleviate suffering and extend lives. We hope that this book can serve as a small stepping stone in this complex process and help the readers to contribute to the improvement of the health of humanity.
New Jersey, February 2022
Xianhai Huang Robert G. Aslanian Wayne H. Tang
List of Contributors
Robert Abel Drug Discovery Group Schrödinger Inc. New York USA
Robert Aslanian Department of Chemistry New Jersey City University Jersey City USA
Corina Becker Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany
Andrea Bortolato Research and Development, Computer‐Assisted Drug Design, Molecular Discovery Technologies Bristol Myers Squibb Princeton USA
David Yu‐Kai Chen Department of Chemistry Seoul National University Seoul South Korea
Yun Ding Encoded Library Technologies/NCE Molecular Discovery GSK Cambridge USA
Wu Du Hinova Pharmaceuticals Inc. Chengdu People’s Republic of China
Markus Follmann Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany
Jeffrey J. Hale Associate Vice President Discovery Chemistry Merck & Co., Inc. West Point USA
Amy Han R&D Chemistry, Therapeutic Proteins Regeneron Pharmaceuticals, Inc. Tarrytown USA
Junliang Hao Discovery Chemistry Research and Technologies Lilly Research Laboratory Eli Lilly and Company Lilly Corporate Center Indianapolis USA
Timothy P. Heffron Discovery Chemistry Genentech, Inc. South San Francisco USA
Xianhai Huang Discovery Chemistry InventisBio Co., Ltd. Florham Park USA Wenping Li Translational Imaging Merck Research Laboratories West Point
