Enzyme Inhibition in Drug Discovery and t: The Good and the Bad

Chuang Lu, PhD , is the Associate Director in the Drug Safety and Disposition Department of Millennium Pharmaceuticals. His current research interests include drug-metabolizing enzymes, drug-drug interaction, and in vitro-in vivo correlation. Albert P. Li, PhD , is the President and CEO of In Vitro ADMET Laboratories, LLC and Advanced Pharmaceutical Sciences, Inc., and the cofounder, Chairman, and CSO of the ADMET Group. His experience spans over twenty-five years in the drug development industry, with over 150 publications. He is the editor of several books, including Drug-Drug Interactions in Pharmaceutical Development , published by Wiley.

PREFACE. CONTRIBUTORS. PART I. DRUG DISCOVERY APPROACHES AND TECHNOLOGIES. 1. The Drug Discovery Process ( Gerald T. Miwa ). 2. Medicinal Chemistry of the Optimization of Enzyme Inhibitors ( Geraldine Harriman, Amy Elder, and Indranath Ghosh ). 3. Bioanalytical Technologies in Drug Discovery ( Jing-Tao Wu ). 4. Safety Biomarkers in Drug Development: Emerging Trends and Implications ( Eric R. Fedyk ). 5. The Role of Drug Metabolism in Drug Discovery ( Tonika Bohnert and Liang-Shang Gan ). 6. Applied Pharmacokinetics in Drug Discovery and Development ( Hua Yang, Xingrong Liu, Anjaneya Chimalakonda, Zheng Lu, Cuiping Chen, Frank Lee, and Wen Chyi Shyu ). PART II. INHIBITION OF THE DRUG METABOLIZING ENZYMES-THE UNDESIRABLE INHIBITION. 7. Enzyme Inhibition and Inactivation: Cytochrome P450 Enzymes ( R. Scott Obach ). 8. Cytochrome P450 Induction ( Edward L. LeCluyse, Michael W. Sinz, Nicola Hewitt, Stephen S. Ferguson, and Jasminder Sahi ). 9. Inhibition of Drug-Metabolizing Enzymes in Gastrointestinal Tract and Its Influence on the Drug-Drug Interaction Prediction ( Aleksandra Galetin and J. Brian Houston ). 10. Enzyme Inhibition in Various In Vitro Systems ( Ping Zhou ). 11. Cytochrome P450 Degradation and Its Clinical Relevance ( Mingxiang Liao, Ping Kang, Bernard P. Murray, and Maria Almira Correia ). 12. Complexities of Working with UDP-Glucuronosyltransferases (UGTs): Focus on Enzyme Inhibition ( Michael B. Fisher ). 13. Evaluation of Inhibitors of Drug Metabolism in Human Hepatocytes ( Albert P. Li and Chuang Lu ). 14. Grapefruit Juice and Its Constituents as New Esterase Inhibitors ( Suresh K. Balani ). 15. Transporter-Xenobiotic Interactions: An Important Aspect of Drug Development Studies ( Gang Luo, Richard Ridgewell, and Thomas Guenthner ). 16. Polymorphisms of Drug Transporters and Their Clinical Implications ( Cindy Q. Xia and Johnny J. Yang ). 17. Clinical Drug Interactions Due to Metabolic Inhibition: Prediction, Assessment, and Interpretation ( Lisa L. von Moltke and David J. Greenblatt ). 18. Predicting Interindividual Variability of Metabolic Drug-Drug Interactions: Identifying the Causes and Accounting for Them Using Systems Approach ( Amin Rostami-Hodjegan ). PART III. INHIBITION OF THE DRUG TARGET ENZYMES-THE DESIRABLE INHIBITION. 19. NF-kappaB: Mechanism, Tumor Biology, and Inhibitors ( Lenny Dang ). 20. G-Protein-Coupled Receptors as Drug Targets ( Wenyan Miao and Lijun Wu ). 21. Pharmacological Modulation of Ion Channels for the Treatment of Chronic Pain ( Yi Liu and Ning Qin ). 22. Targeting the mTOR Pathway for Tumor Therapeutics ( Wei Chen ). 23. HIV-1 Protease Inhibitors as Antiretroviral Agents ( Sergei V. Gulnik, Elena Afonina, and Michael Eissenstat ). INDEX.