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.

Offers essential guidance for discovering and optimizing novel drug therapies Using detailed examples, Evaluation of Enzyme Inhibitors in Drug Discovery equips researchers with the tools needed to apply the science of enzymology and biochemistry to the discovery, optimization, and preclinical development of drugs that work by inhibiting specific enzyme targets. Readers will applaud this book for its clear and practical presentations, including its expert advice on best practices to follow and pitfalls to avoid. This Second Edition brings the book thoroughly up to date with the latest research findings and practices. Updates explore additional forms of enzyme inhibition and special treatments for enzymes that act on macromolecular substrates. Readers will also find new discussions detailing the development and application of the concept of drug-target residence time. Evaluation of Enzyme Inhibitors in Drug Discovery begins by explaining why enzymes are such important drug targets and then examines enzyme reaction mechanisms. The book covers: Reversible modes of inhibitor interactions with enzymes Assay considerations for compound library screening Lead optimization and structure-activity relationships for reversible inhibitors Slow binding and tight binding inhibitors Drug-target residence time Irreversible enzyme inactivators The book ends with a new chapter exploring the application of quantitative biochemical principles to the pharmacologic evaluation of drug candidates during lead optimization and preclinical development. The Second Edition of Evaluation of Enzyme Inhibitors in Drug Discovery continues to offer a treatment of enzymology applied to drug discovery that is quantitative and mathematically rigorous. At the same time, the clear and simple presentations demystify the complex science of enzymology, making the book accessible to many fields— from pharmacology to medicinal chemistry to biophysics to clinical medicine.

The science and applied approaches of enzyme inhibition in drug discovery and development Offering a unique approach that includes both the pharmacologic and pharmaco-kinetic aspects of enzyme inhibition, Enzyme Inhibition in Drug Discovery and Development examines the scientific concepts and experimental approaches related to enzyme inhibition as applied in drug discovery and drug development. With chapters written by over fifty leading experts in their fields, Enzyme Inhibition in Drug Discovery and Development fosters a cross-fertilization of pharmacology, drug metabolism, pharmacokinetics, and toxicology by understanding the "good" inhibitions—desirable pharmacological effects—and "bad" inhibitions—drug–drug interactions and toxicity. The book discusses: The drug discovery process, including drug discovery strategy, medicinal chemistry, analytical chemistry, drug metabolism, pharmacokinetics, and safety biomarker assessment The manipulations of drug metabolizing enzymes and transporters as well as the negative consequences, such as drug–drug interactions The inhibition of several major drug target pathways, such as the GPCR pathway, the NFkB pathway, and the ion channel pathway Through this focused, single-source reference on the fundamentals of drug discovery and development, researchers in drug metabolism and pharmacokinetics (DMPK) will learn and appreciate target biology in drug discovery; discovery biologists and medicinal chemists will also broaden their understanding of DMPK.

-A landmark in the continuously changing world of drugs -Essential reading for scientists and managers in the pharmaceutical industry involved in drug finding, drug development and decision making in the development process -Of use for government institutions and committees working on official guidelines for drug evaluation worldwide

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.

Fully updated and expanded-a solid foundation for understandingexperimental enzymology. This practical, up-to-date survey is designed for a broadspectrum of biological and chemical scientists who are beginning todelve into modern enzymology. Enzymes, Second Editionexplains the structural complexities of proteins and enzymes andthe mechanisms by which enzymes perform their catalytic functions.The book provides illustrative examples from the contemporaryliterature to guide the reader through concepts and data analysisprocedures. Clear, well-written descriptions simplify the complexmathematical treatment of enzyme kinetic data, and numerouscitations at the end of each chapter enable the reader to accessthe primary literature and more in-depth treatments of specifictopics. This Second Edition of Enzymes: A Practical Introductionto Structure, Mechanism, and Data Analysis features refinedand expanded coverage of many concepts, while retaining theintroductory nature of the book. Important new featuresinclude: A new chapter on protein-ligand binding equilibria Expanded coverage of chemical mechanisms in enzyme catalysisand experimental measurements of enzyme activity Updated and refined discussions of enzyme inhibitors andmultiple substrate reactions Coverage of current practical applications to the study ofenzymology Supplemented with appendices providing contact information forsuppliers of reagents and equipment for enzyme studies, as well asa survey of useful Internet sites and computer software forenzymatic data analysis, Enzymes, Second Edition isthe ultimate practical guide for scientists and students inbiochemical, pharmaceutical, biotechnical, medicinal, andagricultural/food-related research.

The past decade has seen the reappearance of natural products as a valuable source of potent therapeutics. Here, experts on bioactive natural products cover the full spectrum of clinically relevant enzymes that are known to be targeted by natural products. Key enzymes include acetylcholine esterase, angiotensin-I-converting enzyme, cyclooxygenase, dihydrofolate reductase, phospholipase A2, respiratory complexes, and many more. By connecting the diversity of medicinal natural product sources with their potential clinical applications, this volume serves as a companion for the medicinal chemist looking for innovative small molecule compounds as well as for pharmacologist interested in the clinical effects and mode of action of herbal and traditional medicines.

Building on the success of the previous editions, Textbook of Drug Design and Discovery has been thoroughly revised and updated to provide a complete source of information on all facets of drug design and discovery for students of chemistry, pharmacy, pharmacology, biochemistry, and medicine. The book follows drug design from the initial lead identification through optimization and structure-activity relationship with reference to the final processes of clinical evaluation and registration. Chapters investigate the design of enzyme inhibitors and drugs for particular cellular targets such as ion channels and receptors, and also explore specific classes of drug such as peptidomimetics, antivirals and anticancer agents. The use of gene technology in pharmaceutical research, computer modeling techniques, and combinatorial approaches are also included.

Drug metabolism and transport are very important facets within the discipline of pharmaceutical sciences, with enzyme kinetic concepts utilized regularly in characterizing and modeling the disposition and elimination of drugs. Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications focuses on very practical aspects of applying kinetic principles to drug metabolizing enzymes and transporters. Divided into five convenient sections, topics include the fundamental principles of enzyme kinetics, the kinetics of oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for both drug metabolizing enzymes and transporters including novel systems biology approaches, understanding of variability both experimental and interindividual (pharmacogenomic), and case studies that provide real life examples of applying these principles. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics especially suitable for the novice, in some cases step-by-step, readily reproducible protocols, and insights to help with troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and easily accessible, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications serves as a very practical teaching tool for novice, non-mathematically trained scientists interested in these fundamental concepts and as an aid for their supervisors in teaching these principles.

An authoritative look at the application of chemical biology in drug discovery and development Based on the award-winning Wiley Encyclopedia of Chemical Biology published in 2008, this book explores the role of chemical biology in drug discovery and development. The first part of the book reviews key principles and techniques used in the design and evaluation of drug candidates. The second part elucidates biological mechanisms of certain diseases, illuminating approaches to investigate and target these diseases. Comprising carefully selected reprints from the Encyclopedia as well as new contributions from leading scholars in the field, this book provides researchers in academia and industry with important information to aid in the development of novel agents to treat disease. Self-contained articles cover a variety of essential topics, including: The design, development, and optimization of drug candidates The pharmacokinetics and properties of drugs Drug transport and delivery Natural products and natural product models as pharmaceuticals Biological mechanisms underlying health and disease Treatment strategies for a range of diseases, from HIV to schizophrenia Chemical Biology is a top-notch guide and reference for anyone working in the areas of drug discovery and development, including researchers in chemical biology and other fields such as biochemistry, medicine, and pharmaceutical sciences.