Contemporary Accounts in Drug Discovery and Development. Группа авторов

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 USA

      Jonathan S. Mason Sosei Heptares Steinmetz Building Granta Park Cambridge UK

      Lothar Roessig Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany

      Laurent Salphati Drug Metabolism and Pharmacokinetics Genentech, Inc. South San Francisco USA

      Peter Sandner Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany

      Tomi Sawyer Maestro Therapeutics Southborough USA

      Sarah K. Scott Encoded Library Technologies/NCE Molecular Discovery GSK Cambridge USA

      Hong C. Shen Department of Medicinal Chemistry, Therapeutic Modalities Roche Innovation Center Shanghai Shanghai People’s Republic of China

      Steven T. Staben Discovery Chemistry Genentech, Inc. South San Francisco USA

      Johannes‐Peter Stasch Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany

      Wayne Haifeng Tang Drug Discovery Group Schrödinger Inc. New York USA

Ling Tong Discovery Chemistry Merck Research Laboratories Kenilworth USA

      Song Yang Department of Medicinal Chemistry Therapeutic Modalities Roche Innovation Center Shanghai Shanghai People’s Republic of China

      Hongying Yun Department of Medicinal Chemistry Therapeutic Modalities Roche Innovation Center Shanghai Shanghai People’s Republic of China

      Wei Zhu Department of Medicinal Chemistry Therapeutic Modalities Roche Innovation Center Shanghai Shanghai People’s Republic of China

      Ning Zou R&D Chemistry, Therapeutic Proteins Regeneron Pharmaceuticals, Inc. Tarrytown USA

1 Current Drug Discovery: Great Challenges and Great Opportunity (an Introduction to Contemporary Accounts in Drug Discovery and Development )

       Jeffrey J. Hale

       Discovery Chemistry, Merck & Co., Inc., 770 Sumneytown Pike, PA 19486‐004, West Point, PA, USA

      As we approach the end of the second decade of the twenty‐first century, global human health faces significant challenges. In May 2018, the World Health Organization (WHO) reported that more than half of recent deaths worldwide were attributable to 10 major causes [1]. Mortality following from cardiovascular disorders, such as ischemic heart disease and stroke, figured prominently on that list, while conditions such as chronic obstructive pulmonary disease, dementias, and diabetes were noted to have increased in frequency since 2000. While the prevalence of deaths from non‐communicable diseases may be perceived to be of greater concern in high‐income countries, the WHO