Our biological system is enriched with enzyme-catalyzed (or enzymatic) reactions that mediate a great multitude of life processes such as gene transcription and metabolism, and the inappropriately up-regulated activity of these enzymatic reactions is a major cause of human diseases such as cancer and metabolic diseases. Therefore, the inhibitors of enzymatic reactions (generally called enzyme inhibitors) constitute a major class of therapeutic agents on the global drug market. One question would then be how to efficiently design enzyme inhibitors. This handbook is the first of its kind in the field, introducing to its readers in a single book the concepts whose exploitation has been demonstrated to be successful in efficiently furnishing effective active site-directed inhibitors for various enzymatic reactions. The book is organized by different concepts and for each concept there is a delineation of its mode of working and its applications with different types of enzymatic reactions. Active Site-directed Enzyme Inhibitors will help its readers to quickly and efficiently obtain effective active site-directed inhibitors for any of the enzymatic reactions under study without a need to resort to library screening- and biostructure-based techniques. This handbook is ideal as an immediate resource for researchers to consult or for students to supplement their study in medicinal chemistry and related courses.

Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecule processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitor and activator, enzyme-catalyzed biotransformation, usage of microbial enzymes, enzymes associated with programmed cell death, natural products as potential enzyme inhibitors, protease inhibitors from plants in insect pest management, peptidases, and renin-angiotensin system. The book provides an overview on basic issues and some of the recent developments in medicinal science and technology. Especially, emphasis is devoted to both experimental and theoretical aspect of modern medicine. The primary target audience for the book includes students, researchers, chemists, molecular biologists, medical doctors, pharmacologists, and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in biochemistry, enzymology, molecular biology, and genetics, many of which are active in biochemical and pharmacological research. I would like to acknowledge the authors for their contribution to the book. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medical approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of pharmacology.

Vital information for discovering and optimizing new drugs "Understanding the data and the experimental details that support it has always been at the heart of good science and the assumption challenging process that leads from good science to drug discovery. This book helps medicinal chemists and pharmacologists to do exactly that in the realm of enzyme inhibitors." -Paul S. Anderson, PhD This publication provides readers with a thorough understanding of enzyme-inhibitor evaluation to assist them in their efforts to discover and optimize novel drug therapies. Key topics such as competitive, noncompetitive, and uncompetitive inhibition, slow binding, tight binding, and the use of Hill coefficients to study reaction stoichiometry are all presented. Examples of key concepts are presented with an emphasis on clinical relevance and practical applications. Targeted to medicinal chemists and pharmacologists, Evaluation of Enzyme Inhibitors in Drug Discovery focuses on the questions that they need to address: * What opportunities for inhibitor interactions with enzyme targets arise from consideration of the catalytic reaction mechanism? * How are inhibitors evaluated for potency, selectivity, and mode of action? * What are the advantages and disadvantages of specific inhibition modalities with respect to efficacy in vivo? * What information do medicinal chemists and pharmacologists need from their biochemistry and enzymology colleagues to effectively pursue lead optimization? Beginning with a discussion of the advantages of enzymes as targets for drug discovery, the publication then explores the reaction mechanisms of enzyme catalysis and the types of interactions that can occur between enzymes and inhibitory molecules that lend themselves to therapeutic use. Next are discussions of mechanistic issues that must be considered when designing enzyme assays for compound library screening and for lead optimization efforts. Finally, the publication delves into special forms of inhibition that are commonly encountered in drug discovery efforts, but can be easily overlooked or misinterpreted. This publication is designed to provide students with a solid foundation in enzymology and its role in drug discovery. Medicinal chemists and pharmacologists can refer to individual chapters as specific issues arise during the course of their ongoing drug discovery efforts.

The remarkable expansion of information leading to a deeper understanding of enzymes on the molecular level necessitated the development of this volume which not only introduces new topics to The Enzymes series but presents new information on some covered in Volume I and II of this edition.