Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research

Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research PDF

Author: M.R. Waterman

Publisher: Springer Science & Business Media

Published: 2013-03-09

Total Pages: 235

ISBN-13: 3662030195

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Metabolic research and especially that which focuses on the monooxygenase cytochrome P450 system has gone through dramatic progressive changes within the last decade. Availability of highly sophisticated analytical techniques has contributed to increased molecular understanding of biotransformation pathways. Nowadays designer drugs are computer composable focussing on metabolic stability. The rapid development of recombinant enzymes has, in many cases, replaced the intensive work on P450 isolation from naturally occurring sources. Recombinant P450s can be expressed in cell lines and thus made available for reproducible and constant use addressig a large number of scientific questions. This book describes the present position of such research.

Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research

Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research PDF

Author: M.R. Waterman

Publisher: Springer

Published: 1994-10-31

Total Pages: 227

ISBN-13: 9783540583431

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Metabolic research and especially that which focuses on the monooxygenase cytochrome P450 system has gone through dramatic progressive changes within the last decade. Availability of highly sophisticated analytical techniques has contributed to increased molecular understanding of biotransformation pathways. Nowadays designer drugs are computer composable focussing on metabolic stability. The rapid development of recombinant enzymes has, in many cases, replaced the intensive work on P450 isolation from naturally occurring sources. Recombinant P450s can be expressed in cell lines and thus made available for reproducible and constant use addressig a large number of scientific questions. This book describes the present position of such research.

Cytochromes P450

Cytochromes P450 PDF

Author: Costas Ioannides

Publisher: Royal Society of Chemistry

Published: 2008-06-27

Total Pages: 538

ISBN-13: 1847558429

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During half a century, cytochrome P450 in its original uniqueness as an optically "wrong" cytochrome has attracted many investigators, who have contributed to the unveiling of a bewildering multiplicity of biologically important functions of the, by now very large, superfamily of cytochrome P 450 enzymes. With its discovery in 1958 and with the advent of more refined spectroscopic methodologies, through the double wavelength spectrophotometry, the mysterious enzyme system began to reveal its secrets in a swift stream of investigative successes. As one of the most extensively studied enzyme systems worldwide the interest in cytochromes P450 very much reflects its importance in the elimination of drugs and other chemicals from the body and its role in chemical toxicity and in the aetiology of diseases such as cancer. There has been significant progress in research in this area in recent years and current books on this subject are now out of date. This much needed, new, fully up-to-date publication fills this gap and emphasises the new relevant topics that have emerged during the last decade in an easily accessible manner. The enzyme system, cytochromes P450, comprises a number of families/subfamilies, and the focus of the book is to deal with each individually, furnishing information directly relevant to scientists involved in the development of chemicals, in particular in the evaluation of their safety. The book has contributions from internationally respected scientists who are research-active in the relevant areas. The authors have made extensive use of figures and tables so that the reader can access the necessary information without always having to read the text. In addition, a very extensive, user-friendly index is a unique hallmark of the book. Part A of this monograph introduces the reader to the current knowledge of the evolutionary development of cytochrome P450 structure and function. Furthermore, it deals with the role of this enzyme in the formation of reactive intermediates. The shrewd and extensive utilisation of the molecular biology methodology very rapidly led to a vast body of enzymes calling for a classification of the plethora of different cytochromes P450 (the superfamily) into families and subfamilies. This is aptly exemplified by the ten chapters in Part B of this book, dealing with ten subfamilies and two families of cytochrome P450. Part C offers an insight into another aspect of cytochrome P450 research, namely its regulation through receptor-mediated stimuli - as opposed to enzyme induction or inhibition. The final chapter translates the current data on one of several drug metabolising systems into clinical application and highlights the role of cytochromes P450 in the treatment of neoplastic growth. The book deals extensively with each family/subfamily of the cytochromes P450 that contribute to the metabolism of xenobiotics. Essential and invaluable information is provided for the industrial research scientist working with fine chemicals, and especially those in the pharmaceutical industry, dealing with the safety evaluation of chemicals or being involved in the study of their metabolism, pharmacokinetics and toxicological properties. It should also prove of interest to Regulators concerned with the safety evaluation of chemicals, research pharmacologists and toxicologists, and postgraduate students studying drug metabolism and toxicology at an advanced level.

Enzyme Inhibition in Drug Discovery and Development

Enzyme Inhibition in Drug Discovery and Development PDF

Author: Chuang Lu

Publisher: John Wiley & Sons

Published: 2010-01-26

Total Pages: 878

ISBN-13: 0470538945

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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.

Cytochrome P450

Cytochrome P450 PDF

Author: Paul R. Ortiz de Montellano

Publisher: Springer Science & Business Media

Published: 2007-02-05

Total Pages: 702

ISBN-13: 0387274472

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Cytochrome P450: Structure, Mechanism, and Biochemistry, third edition is a revision of a review that summarizes the current state of research in the field of drug metabolism. The emphasis is on structure, mechanism, biochemistry, and regulation. Coverage is interdisciplinary, ranging from bioinorganic chemistry of cytochrome P450 to its relevance in human medicine. Each chapter provides an in-depth review of a given topic, but concentrates on advances of the last 10 years.

Drug Metabolizing Enzymes

Drug Metabolizing Enzymes PDF

Author: Jae Lee

Publisher: CRC Press

Published: 2003-09-03

Total Pages: 608

ISBN-13: 9780824742935

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Critical in the elimination of drugs and other xenobiotics from the body, cytochrome P450 has strong bearing on scientific assessments of genetic polymorphism in metabolism, possible drug-drug interactions, and bioavailability of candidate drugs. This text systematizes findings on P450 and similar enzymes - as well as parallel issues shaping the pharmaceutical industry - to promote the next generation of safer, more effective drugs.

Encyclopedia of Cancer

Encyclopedia of Cancer PDF

Author: Manfred Schwab

Publisher: Springer Science & Business Media

Published: 2008-09-23

Total Pages: 3307

ISBN-13: 3540368477

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This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.

Pharmacology and Toxicology of Cytochrome P450 - 60th Anniversary

Pharmacology and Toxicology of Cytochrome P450 - 60th Anniversary PDF

Author: Hiroshi Yamazaki

Publisher: Elsevier

Published: 2022-08-09

Total Pages: 434

ISBN-13: 0323911099

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This volume highlights the extensive contributions by worldwide researchers in the cytochrome P450 (P450) field over past six decades since the first article on P450 was published in 1962. Research on many forms of P450s has been extended into different fields, from molecules to in vivo situations, because pharmacologists and toxicologists appreciate and are attracted to the potential therapeutics. The purpose of this volume was to collect a comprehensive description of major progress to date, to discuss the possible future directions, and to invite young researchers to join this important and exciting world of P450.

Metabolism of Drugs and Other Xenobiotics

Metabolism of Drugs and Other Xenobiotics PDF

Author: Pavel Anzenbacher

Publisher: John Wiley & Sons

Published: 2012-05-29

Total Pages: 755

ISBN-13: 352732903X

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A practice-oriented desktop reference for medical professionals, toxicologists and pharmaceutical researchers, this handbook provides systematic coverage of the metabolic pathways of all major classes of xenobiotics in the human body. The first part comprehensively reviews the main enzyme systems involved in biotransformation and how they are orchestrated in the body, while parts two to four cover the three main classes of xenobiotics: drugs, natural products, environmental pollutants. The part on drugs includes more than 300 substances from five major therapeutic groups (central nervous system, cardiovascular system, cancer, infection, and pain) as well as most drugs of abuse including nicotine, alcohol and "designer" drugs. Selected, well-documented case studies from the most important xenobiotics classes illustrate general principles of metabolism, making this equally useful for teaching courses on pharmacology, drug metabolism or molecular toxicology. Of particular interest, and unique to this volume is the inclusion of a wide range of additional xenobiotic compounds, including food supplements, herbal preparations, and agrochemicals.