Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists [Kindle Edition]
Author: Robert A. Copeland | Language: English | ISBN: B00B9W34EW | Format: PDF, EPUB
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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. Books with free ebook downloads available Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists
- File Size: 5939 KB
- Print Length: 572 pages
- Publisher: Wiley-Interscience; 2 edition (January 31, 2013)
- Sold by: Amazon Digital Services, Inc.
- Language: English
- ASIN: B00B9W34EW
- Text-to-Speech: Enabled
- Lending: Enabled
- Amazon Best Sellers Rank: #1,077,223 Paid in Kindle Store (See Top 100 Paid in Kindle Store)
There are numerous books on the market on enzyme kinetics, enzymology and protein-ligand interactions. This one is pretty superficial. A good example of the superficial approach it total misleading chapter on processive enzymes.
The authors idea that the lack of captured unprocessive intermediates is a proof of processivity is naive (i.e. the absence of evidence is not an evidence of absence). The author has cited JBC study by Hermann et. al. as an example of processivity with human DNA methyltransfertase. This enzyme has the steady-state turnover rates of less than 0.5h-1! The first turnover rates in best case scenario takes about 20 minutes! Thus, there is no even theoretical chance that human DNA methyltransferase can make more two turnovers in 2 hours, and certainly cannot be a processive enzyme. Moreover, the JBC study by Herman et. al. expressed the enzyme activity in raw cpms, thus the authors do not have any idea how much product and catalytic turnovers their enzyme has. I do not blame the authors of the JBC study for the amateurish failures, they are not experts in enzymology. However, if somebody is writing a book in enzymology and enzyme kinetics, than such oversight is inexcusable. The book by Alan Fersht is a good example of a knowledgeable description of quantitative analysis of processive enzymes. Pulse-chase approach with equations given in Alan Fersht's book are much simpler, more reliable and more quantitative approach for the studies of enzyme processivity.
In summary the book by Robert Allen Copeland gives little bit of everything but at the end it gives nothing. If you need to study protein-ligand interactions go with one of these books:
1. Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting.
This new edition of "Evaluating Enzyme Inhibitors in Drug Discovery" by Dr. Copeland expands the scope of his first edition to include chapters on drug-target residence time and quantitative pharmacology. Each of these is a worthy addition to an already extremely useful compendium. It is worth understanding the favorable and unique positioning that the first edition of this book has had among the community of drug-discovery researchers. As stated in the introduction, the target audience is expected to encompass a diverse group of drug discovery scientists, rather than particularly expert enzymologists. There are other texts that convey individual aspects of enzymology and inhibitor action to deeper depths (e.g. Segel, Fersht, Cornish-Bowden and others), and these are referenced accordingly. The clear and logical coverage of material is unsurpassed for applying a context for understanding what types of questions should be explored for drug discovery. As an example, in my own experience working with multidisciplinary drug-discovery teams, the concept of understanding inhibition modality (which narrows down inhibitor action to a family of similar inhibition mechanisms) is extremely fruitful-- and this text has been the go-to source for helping introduce these concepts among colleagues including beginning enzymologists, medicinal chemists, and others.
The addition of sections on drug-target residence time and quantitative pharmacology are other advancements that are valuable additions to the text. As more pre-clinical drug candidates are being pursued exactly to exploit residence time and thereby impact dosing strategies, the inclusion of solid explanations about these areas are essential reading. In summary, this text is a great resource on the area it surveys.
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