Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists

This text lays out a detailed framework for the use of enzyme kinetics in the drug discovery process. Well written and informative covering the various drug binding mechanisms as well as an excellent chapter on tight binding inhibitors (similar to the 1st edition). The 2nd edition has a lot to offer over the 1st ed. - I found the new chapters with examples of target occupancy assays as well as the importance drug target residence times very informative and unlike any other book I have encountered on this subject.Definitely worth getting this new edition if you have the 1st ed. excellent for biochemist, biologist and chemist working in the drug discovery field.

Dr. Copeland is widely known for his expertise in the quantitative evaluation and characterization of enzyme inhibitors, and I found myself frequently citing or referring to the first edition of this book in my graduate level class on Drug Discovery. I was therefore interested to learn that a new edition had been published. Having spent many years in industry before moving to academia, I have been looking for a book that could capture the key ideas, theory and techniques that are necessary to equip advanced undergraduate or graduate students to understand the biochemical side of small molecule drug discovery.The new (second) edition is simply superb. Particular strengths include:1) Excellent balance between theoretical aspects of enzyme and inhibitor action, and more practical issues such as assay design, SAR and ADME.2) Clear and rigorous treatment of the quantitative analysis of experimental inhibition data, in all its common variants and permutations.3) Detailed consideration of target residence time and also covalent inhibition, reflecting the increasing importance of these concepts for drug discovery.4) Incorporation throughout the text of the notion that proteins are flexible, adaptive molecules, and the implications of this fact for inhibitor design and evaluation.I don't know of any other book that so effectively marries the theory and practice of drug discovery as it applies to enzyme inhibitors. As such, it differs fundamentally from more "academic" enzymology texts. Incorporation of well chosen "key learning points" at the beginning of each chapter adds to the value of the book as a teaching and learning resource. The only feature I don't particularly like is that the color illustrations are all collected in the middle of the book, rather than being placed at the relevant points of the text. This is only a minor annoyance, however.I wish a book like this had existed to guide me when I first entered the drug discovery industry, and am thrilled now to find a text that so exactly captures so many important concepts for drug discovery. I plan to use the second edition as a text for future iterations of my class, and will also be recommending it to friends who work in industry as a reference, for its rigorous yet clear exposition of so many key concepts, approaches and techniques.

I was a fan of the first edition because of its practical orientation to researchers testing inhibitors in the laboratory. Nothing in the book is irrelevant to those looking for small molecule inhibitors of an enzyme or receptor. The small format of its 265 pages of text also made it less intimidating that the big treatises on enzyme kinetics, without sacrificing rigor and using real examples from drug discovery to illustrate concepts. This made it ideal for introducing junior team members and graduate students to the subject, not to mention my own re-learning of deficiently remembered topics. This second edition maintains the same format and practical orientation, but it has grown now to 465 text pages, mainly because of the addition of two new chapters. The first one is about "Drug target residence time", a critical concept for drug discoverers when working through differences in compound efficacy inexplicable by the more usual Ki or IC50 parameters. The second one is titled "Quantitative biochemistry in the pharmacological evaluation of drugs". In the spirit of this book, the new chapter succinctly communicates all the background needed to understand a pharmacologist's contribution to a drug discovery team. The meaning and impact of basic pharmacokinetic parameters on drug developability are clearly explained with examples, along with concepts such as bioavailability, protein binding, cytochrome P450 interactions or QTc prolongation. In summary, this is a must-have book for anyone introducing him or herself, or others, to target-based drug discovery.

Simply stated, this book is a required text for anyone interested in understanding and mastering lead discovery and optimization. The use of clear, concise language coupled with practical, illustrative examples is highly effective in breaking down the wide range of technical hurdles encountered in these critical phases of drug discovery. As someone who has both taught graduate level courses and supervised an industrial biochemistry department focused on these areas, I can attest that this book is both an excellent primer for individuals that are new to drug discovery and an essential reference for experienced practitioners looking for a quick refresher on more detailed areas such as tight-binding inhibition or slow-dissociation kinetics. For me, the key measure of any scientific text is the time any text spends on the shelf rather than in hands of an interested reader. By this measure the first edition was a tremendous success in that, as a department head, we had to order three copies for each member of the department because interested scientists from other departments (medicinal chemistry, cellular biology) were continually "borrowing" the texts and retaining the copies. I expect that the new chapters covering the topics of drug-target residence time and drug metabolism will only make this "problem" worse since they follow in the same approachable style and significantly extend the reach of the previous edition and significantly increase the overall utility and value. My recommendation: buy one for yourself and have one on hand to lend!