7650 Journal of Medicinal Chemistry, 2008, Vol. 51, No. 23
Book ReViews
Book ReViews High-Throughput Lead Optimization in Drug Discovery. By Tushar Kshirsagar. CRC Press, Taylor and Francis Group, Boca Raton, FL. 2008. viii + 243 pp. 18 × 26 cm. ISBN 0849372682. $149.95. Like many technologies aimed at improving the drug discovery process but that are invariably overhyped, combinatorial chemistry exploded onto the scene in the late 1970s and created unrealistic expectations. The technology has now matured to become an additional valuable tool in the medicinal chemist’s arsenal in the search for new medicines and is applicable at different stages in the drug discovery process. This book is the fourth in a series of monographs in molecular diversity and combinatorial chemistry, high-throughput discovery, and associated technologies, in the series Critical ReViews in Combinatorial Chemistry edited by B. Yan and A. W. Czarnik. The field of combinatorial chemistry or parallel synthesis that has evolved over the past 10 years is an area of both industrial and academic interest. The individual contributors to this book are drawn primarily from academia, but the biotechnology industry is also represented. The book consists of nine chapters that are primarily individual “war stories” illustrating the use of parallel synthetic approaches to address a variety of problems in the drug discovery area. Chapter 1 provides a comprehensive introduction and review of the period 2000-2005 where combinatorial chemistry was successfully applied primarily for the optimization of small molecule drugs. This chapter illustrates the approach with examples chosen from a wide variety of therapeutic indications and biochemical mechanisms. The typical format is one where the biochemical background is succinctly summarized and the progression from “hit” to optimized lead is illustrated followed by a brief conclusion. Chapter 2 covers the application of parallel synthesis to the problems of modulating protein-protein interactions, notoriously difficult areas for small molecule inhibitors, but the authors demonstrate that by combination of parallel synthesis with high-quality X-ray/NMR data of proteins, significant progress can be made. Chapter 3 describes a number of case studies in the application of parallel synthesis to hit identification, hit exploration, hit to lead, and lead optimization aspects of the drug discovery process, and the chapter explores the concept of multicomponent reactions, a technique that allows for the synthesis of a large number of cores structures. Chapters 4-9 provide examples in a variety of therapeutic areas and biochemical mechanisms involving solid-phase synthesis, solution based synthesis, or a mixture of the two techniques.
aid in the drug discovery process in the search for newer and better drugs. It may be also read with interest and profit by medicinal chemists who are interested in learning of real world applicability of the technology. Jan W. F. Wasley Simpharma LLC 1 Stone Fence Lane Guilford, Connecticut 06437 JM801068Z 10.1021/jm801068z
Annual Review of Biochemistry. Volume 77. Edited by Roger D. Kornberg , Christian R. H. Raetz , James E. Rothman , and Jeremy W. Thorner. Annual Reviews, Inc., Palo Alto, CA. 2008. x + 815 pp. 19.5 × 24 cm. ISBN 978-0-8243-0877-8. $89.00. This Annual Review of Biochemistry features 29 expert reviews on significant developments in biochemistry and two prefatory chapters describing the background, science, and unique perspectives of two well-known scientists. In addition, this volume includes a cumulative index of contributing authors and chapter titles for Volumes 73-77. The chapters provide thorough reviews of various research topics in biochemistry, describing recent findings as well as remaining questions. This volume features a section entitled, “Single-Molecule Theme”, comprising an introductory chapter (i.e., “In Singulo Biochemistry: When Less Is More”) and seven reviews on several research areas (e.g., RNA and protein folding) impacted by new and novel single-molecule methods. Both the methodology and the recent findings in single-molecule biochemistry are presented clearly in significant detail. The majority of the volume is composed of a section entitled, “Recent Advances in Biochemistry”, which includes 21 chapters on a variety of topics, ranging from recent discoveries to novel methodologies. While the focus of these reviews is on basic biochemistry, many of the chapters (e.g., “Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry”, “CFTR Function and Prospects for Therapy”, and “Cellular Defenses against Superoxide and Hydrogen Peroxide”) relate the newly acquired information to human disease and drug targets. Therefore, this Volume will appeal to those in a variety of biomedical fields, including medicinal chemistry, pharmacology, and toxicology.
This book is very much a series of individual reviews of specific applications of the parallel synthesis technology, and one of the consequences is that in the introduction to each chapter the chronology of the transition of combinatorial chemistry technology from one of “large number of compounds” to “targeted compounds of higher quality” is constantly restated.
As mentioned above, the book includes two prefatory chapters (i.e., “Discovery of G-Protein Signaling” and “Moments of Discovery”) that are both educational and enjoyable to read. In each, the life history and scientific development for each influential researcher are portrayed as a peregrination leading to key findings and, ultimately, great discoveries.
Overall, this book is a successful attempt to provide in one volume many illustrative examples in this evolving field and it presents a wealth of information on topics that demonstrate the versatility and power of the technology. It is an instructive book for those scientists interested in new developments and tools to
The chapters are well-written and are well-organized into titled sections that contain numerous colorful figures and detailed legends. Each review includes ample background and explanation such that those who are not familiar with the topic will ultimately learn and benefit from reading. In addition, the
Book ReViews
concluding “Summary Points” and “Future Issues” sections for the chapters as well as the numerous definitions found in the margin are extremely helpful. Given these qualities and characteristics, this book may serve not only as an excellent resource for researchers but also as an invaluable tool for educators. In summary, the reviews in this book are well-written and succinct and yet adequately detailed. Volume 77 is an excellent addition to the long-running series, and it will be a superb resource, not only for biochemists, but also for those in related
Journal of Medicinal Chemistry, 2008, Vol. 51, No. 23 7651
biomedical fields. In addition, given the high quality and quantity of content, the book is an exceptional value for its price. Jonathan A. Doorn DiVision of Medicinal and Natural Products Chemistry College of Pharmacy UniVersity of Iowa Iowa City, Iowa 52242 JM801287B 10.1021/jm801287b
