Drug Metabolism Handbook

Concepts and Applications in Cancer Research
Herausgegeben:Nassar, Ala F.; Hollenberg, Paul F.; Scatina, JoAnn; Kanti Manna, Soumen; Zeng, Su

• Gebundenes Buch

Produktbeschreibung

Mit der neu überarbeiteten zweiten Auflage von Drug Metabolism Handbook: Concepts and Applications in Cancer Research legt ein anerkanntes Team von Wissenschaftlern eine prägnante, solide Betrachtung des Arzneimittelmetabolismus vor und präsentiert mit zahlreichen Illustrationen und detaillierten Erklärungen die neuesten Werkzeuge und Techniken, die in der Forschung, Pharmakologie und Medizin verwendet werden. In diesem Buch werden die Schaffung neuer molekularer Einheiten, die Entwicklung von Arzneimitteln, die Fehlerbehebung und andere äußerst relevante Konzepte besprochen, um der Leserschaft neue Anwendungen in der Forschung, Entwicklung und Bewertung von Arzneimitteln nahezubringen.

Die neueste Ausgabe enthält aktualisierte Inhalte zu den Grundlagen des Metabolismus und zur Anwendung verschiedener neuer Techniken wie Massenspektrometrie, bildgebender Verfahren, Metabolomik und Immuntherapie in der Krebsbehandlung. Darüber hinaus wird in ausführlichen Fallstudien die Rolle des Metabolismus in der Arzneimittelentwicklung betrachtet.

Außerdem bietet das Werk:
_ Eine gründliche Einführung in den Arzneimittelmetabolismus, auch aus historischer Sicht, sowie Erläuterungen zu Faktoren, die den Metabolismus beeinflussen, und zu Biotransformationen im Arzneimittelmetabolismus
_ Umfassende Erörterungen der Technologien für In-vitro- und In-vivo-Studien, insbesondere der Massenspektrometrie und der beschleunigten Identifizierung von Metaboliten durch Massenspektrometrie
_ Eine eingehende Untersuchung der Arzneimittelinteraktionen, insbesondere der Enzymhemmung und der Inhibition mithilfe des Cytochrom-P450-Systems
_ Ausführliche Erläuterungen zur Toxizität von Arzneimitteln sowie zur Rolle des Arzneimittelmetabolismus bei der Toxizität und zu allergischen Reaktionen auf Arzneimittel

Produktdetails

• Verlag: Wiley / Wiley & Sons
• Artikelnr. des Verlages: 1W119851010
• 2. Aufl.
• Seitenzahl: 1056
• Erscheinungstermin: 22. November 2022
• Englisch
• Abmessung: 238mm x 167mm x 60mm
• Gewicht: 1970g
• ISBN-13: 9781119851011
• ISBN-10: 1119851017
• Artikelnr.: 64229070

Autorenporträt

Ala F. Nassar, PhD, is a faculty member at Yale University. He leads and executes ADME-Tox experiments supporting grant projects. He has served on numerous editorial boards and is the editor of the previous edition of Drug Metabolism Handbook: Concepts and Applications and Biotransformation and Metabolite Elucidation of Xenobiotics: Characterization and Identification. Paul F. Hollenberg, PhD, was the Maurice H. Seevers Professor and Chair of Pharmacology at the University of Michigan for more than 20 years. His research focused on the active sites of P450s and their catalytic function. He was cofounder and Associate Editor of Chemical Research in Toxicology and has served on numerous editorial boards and review panels. JoAnn Scatina, PhD has over 30 years of experience in Drug Metabolism and Preclinical Drug Development with leadership roles in both big pharma (Wyeth) and smaller biotech firms. She also provides expert drug development advice as a consultant to biotech and academic institutions. Soumen Kanti Manna, PhD, is an Associate Professor in the Biophysics and Structural Genomics Division of Saha Institute of Nuclear Physics, Kolkata. His doctoral work involved cytochrome P450 and other metalloproteins. His current research activities include unravelling of metabolic reprogramming associated with gene-environment interaction and cancer as well as RNA modification and biomarker discovery. Su Zeng, PhD, is a Professor and Director of Institute of Drug Metabolism and Pharmaceutical Analysis at College of Pharmaceutical Sciences, Zhejiang University. His research focuses on the regulation mechanism of drug ADME-Tox by using epigenetic models, transgenic cells expressing drug metabolizing enzymes, or transporters.

Inhaltsangabe

Volume 1

Preface xiii

List of contributors xv

Part I. Introduction 1

1. Historical Perspective 3
Roberta S. King

1.1 Controversies Spanning Past, Present, and Future 3

1.2 1800s: Discovery of Major Drug Metabolism Pathways (Conti and Bickel, 1977) 5

1.3 1900-1950s: Confirmation of Major Pathways and Mechanistic Studies 8

1.4 1950s-1980: Modern Drug Metabolism Emerges, with Enzymatic Basis 9

1.5 1980-2005: Field Driven by Improved Technologies 10

1.6 2005+: High Technology 10

References 10

2. Factors Affecting Metabolism 13
Roberta S. King

References 16

3. Biotransformations in Drug Metabolism 17
Roberta S. King

3.1 Drug Metabolism in Drug Development and Drug Therapy 17

3.2 Prediction of Metabolite and Enzyme Responsible 20

3.3 Functional Group Biotransformations: Phase I, Phase II, and Catalysis 21

3.4 Oxidations and Cytochrome P450 23

3.5 Enzymology and Modifiers of Cytochrome P450s 34

References 39

4. A Comprehensive Picture of Biotransformation in Drug Discovery 41
Joe R. Cannon, Prakash Vachaspati, and Yang Yuan

4.1 Introduction 41

4.2 Rate of Metabolism 43

4.3 Metabolism of Small Molecules 46

4.4 Analytical Technologies in Drug Metabolism 65

4.5 Biotransformation for Novel Modalities - Peptides and Protein Degraders 79

4.6 Conclusion 93

References 93

5. In Vivo Drug Metabolite Kinetics 103
Zheng Yang

5.1 Introduction 103

5.2 In Vivo Drug Metabolite Kinetic Concepts and Principles 105

5.3 Effect of Inhibition and Induction on Metabolite Kinetics 122

5.4 Determination of Formation and Elimination Clearance of

Metabolite 127

5.5 Incorporation of Pharmacologically Active Metabolite(s) in

Pharmacokinetic/Pharmacodynamic Modeling 130

5.6 Summary 135

Abbreviations 135

References 137

6. LC-MS/MS-Based Proteomics Methods for Quantifying Drug-Metabolizing Enzymes and Transporters 143
Logan S. Smith, Sun Min Jung, Jiapeng Li, and Hao-Jie Zhu

6.1 Introduction 143

6.2 Mass Spectrometry Versus Alternative Protein Quantification Methods 144

6.3 Mass Spectrometry Data Acquisition Methods for Proteomics Analysis 145

6.4 Targeted Approaches 146

6.5 Untargeted Proteomics Approaches 147

6.6 Relative Quantification Versus Absolute Quantification 150

6.7 Label-Based Proteomics 152

6.8 Label-Free Proteomics 155

6.9 DMET Protein Quantification Using LC-MS/MS-Based Proteomics 158

6.10 Potential Application of DMET Expression Studies 160

6.11 Considerations of DMET Protein Quantification Utilizing LC-MS/MS Methods 163

6.12 Conclusion 164

References 164

Part II. Technologies for in vitro and in vivo studies 177

7. Mass Spectrometry 179
Thomas R. Sharp

7.1 Introduction 179

7.2 A Brief History 180

7.3 The Mass Spectrometry Literature 182

7.4 Mass Spectrometry Instrumentation 183

7.5 Interpretation:What Does it Mean 211

7.6 Conclusions 254

References 255

8. Accelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward 267
Ala F. Nassar

8.1 Introduction 267

8.2 Criteria for LC-MS Methods 269

8.3 Matrices Effect 269

8.4 Tool of Choice for Metabolite Characterization 270

8.5 Strategies for Identifying Unknown