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Preface

It has been almost nine years now since the publication of the first edition of Case Studies in Modern Drug Discovery and Development in 2012. The book has been well received, in part for its breadth of topics including accounts of the discovery of life‐saving drugs. The purpose of the first edition of the book was to preserve knowledge of drug discovery and development at a time that small‐molecule drug discovery was seemingly at a crossroad and looking for direction. In the years since the publication of the first edition, we have been fortunate to witness the approval of many new drug products. In fact, 2018 witnessed a historic number of novel drug approvals by the FDA (a total of 59). Technology has advanced at an amazing pace in the past few years, which has enabled many formally untenable modalities, such as peptides, drug conjugates, antibodies, RNA, and vaccines, to provide new options for drug discovery. In addition, advances in basic science have also helped to accelerate the drug discovery process. 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

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