Enzymes and Their Inhibitors: Drug Development (Enzyme Inhibitors)

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Focusing on the development of enzyme inhibitors as therapeutic drugs, Enzymes and Their Inhibitors: Drug Development provides a concise overview of the chemistry of major types of enzymes and their inhibitors. The opening chapters introduce readers to the structure, functions, mechanisms, and kinetics of enzymes, including their use as disease markers, analytical reagents, and in industrial processes. Subsequent chapters discuss the different types of enzyme inhibitors and the principles involved in developing them into effective drugs. This outstanding text, also valuable as a professional reference, will be useful to all students of pharmacology and medicinal chemistry.

Enzymes and Their Inhibitors: Drug Development (Enzyme Inhibitors) Review

This is a book of five chapters, but the last occupies about 45% of the length of the book, and is clearly the main focus of interest. The others deal with enzyme structure, mechanisms, kinetics, and inhibition, and provide accounts of these topics similar to what one can find in a hundred other books. They were all written by different authors and there is no sign that there was any editing, so they repeat one another to some degree, using different symbols for the same thing, or sometimes the same symbol for different things. The chapter on elementary kinetics includes the usual error of suggesting that an enzyme reaches its limiting rate at a substrate concentration of about twenty times its Michaelis constant, and is totally confused about the conditions in which the Michaelis constant may be taken as approximately equal to the substrate dissociation constant. The chapter on structure (and indeed the whole book) is vague about ionic structures, sometimes remembering that carboxylic acids and aliphatic amines ionize, and sometimes not. This fault is found in so many books that it may seem hardly worth mentioning, but it puzzles me greatly that it remains so widespread, especially in a book about drug design. How can one understand anything about mechanisms of inhibition if one has no idea about what charges are likely to be present? How can one begin to guess whether a drug will be absorbed from the intestine if one has no idea whether it will be a neutral molecule at neutral pH?

The last chapter, on the development of enzyme inhibitors as drugs, clearly supplies the main reason why one might buy the book. It was mainly written by the editors, who must surely have known what the earlier chapters were about, but it repeats much of the basic information on kinetics and inhibition. In this context the authors could have clarified the meaning of the concentration for half-inhibition (and its relationship to an inhibition constant), but they do not. In the text they do give a half-hearted warning about the dangers of taking it too seriously, but this is effectively contradicted by the much more prominent table on the same page.

There is a great deal of detailed information about particular inhibitors used or intended as drugs, the enzymes they inhibit, and the diseases they are supposed to combat. As a compilation of this kind of information the book is certainly useful.

I was hoping that this book might convince me that rational drug design was becoming more of a reality and less of a catchphrase, but there is little sign of that. Most successful drugs are still found by making a series of variations on structures discovered more or less by chance. There are doubtless many reasons for this, but one of them is surely a reluctance to take metabolism seriously: what keeps organisms going is metabolism, and what (many) drugs do is to alter metabolism. When people writing about drug design remember to mention metabolism at all, they seem to regard it mainly as an unfortunate tendency of organisms to change drugs into other things; recognition that the enzymes to be inhibited by drugs are themselves elements of metabolism is rare. There is a revealing comment to the effect that "careless transcription" in viruses leads to drug resistance. Imputing carelessness to a virus is weird enough to start with, but supposing that a virus is being careless when it survives, failing to do the bidding of a drug company, is weirder still.

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