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 "e;good"e; inhibitions desirable pharmacological effects and "e;bad"e; 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.

The science and applied approaches of enzyme inhibition in drugdiscovery and developmentOffering a unique approach that includes both the pharmacologicand pharmaco-kinetic aspects of enzyme inhibition, EnzymeInhibition in Drug Discovery and Development examines thescientific concepts and experimental approaches related to enzymeinhibition as applied in drug discovery and drug development.With chapters written by over fifty leading experts in theirfields, Enzyme Inhibition in Drug Discovery and Developmentfosters a cross-fertilization of pharmacology, drug metabolismpharmacokinetics, and toxicology by understanding the "good"inhibitions--desirable pharmacological effects--and "bad"inhibitions--drug-drug interactions and toxicity. Thebook discusses:* The drug discovery process, including drug discovery strategymedicinal chemistry, analytical chemistry, drug metabolismpharmacokinetics, and safety biomarker assessment* The manipulations of drug metabolizing enzymes and transportersas well as the negative consequences, such as drug-druginteractions* The inhibition of several major drug target pathways, such asthe GPCR pathway, the NFkB pathway, and the ion channel pathwayThrough this focused, single-source reference on thefundamentals of drug discovery and development, researchers in drugmetabolism and pharmacokinetics (DMPK) will learn and appreciatetarget biology in drug discovery; discovery biologists andmedicinal chemists will also broaden their understanding ofDMPK.

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-TaoWu).4. Safety Biomarkers in Drug Development: Emerging Trends andImplications (Eric R. Fedyk).5. The Role of Drug Metabolism in Drug Discovery (TonikaBohnert and Liang-Shang Gan).6. Applied Pharmacokinetics in Drug Discovery and Development(Hua Yang, Xingrong Liu, Anjaneya Chimalakonda, Zheng LuCuiping Chen, Frank Lee, and Wen Chyi Shyu).PART II. INHIBITION OF THE DRUG METABOLIZINGENZYMES--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 JasminderSahi).9. Inhibition of Drug-Metabolizing Enzymes in GastrointestinalTract and Its Influence on the Drug-Drug InteractionPrediction (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 AlmiraCorreia).12. Complexities of Working withUDP-Glucuronosyltransferases (UGTs): Focus on Enzyme Inhibition(Michael B. Fisher).13. Evaluation of Inhibitors of Drug Metabolism in HumanHepatocytes (Albert P. Li and Chuang Lu).14. Grapefruit Juice and Its Constituents as New EsteraseInhibitors (Suresh K. Balani).15. Transporter-Xenobiotic Interactions: An ImportantAspect of Drug Development Studies (Gang Luo, Richard Ridgewelland Thomas Guenthner).16. Polymorphisms of Drug Transporters and Their ClinicalImplications (Cindy Q. Xia and Johnny J. Yang).17. Clinical Drug Interactions Due to Metabolic Inhibition:Prediction, Assessment, and Interpretation (Lisa L. von Moltkeand David J. Greenblatt).18. Predicting Interindividual Variability of MetabolicDrug-Drug Interactions: Identifying the Causes and Accountingfor Them Using Systems Approach (Amin Rostami-Hodjegan).PART III. INHIBITION OF THE DRUG TARGET ENZYMES--THEDESIRABLE INHIBITION.19. NF-kappaB: Mechanism, Tumor Biology, and Inhibitors(Lenny Dang).20. G-Protein-Coupled Receptors as Drug Targets (Wenyan Miaoand Lijun Wu).21. Pharmacological Modulation of Ion Channels for the Treatmentof Chronic Pain (Yi Liu and Ning Qin).22. Targeting the mTOR Pathway for Tumor Therapeutics (WeiChen).23. HIV-1 Protease Inhibitors as Antiretroviral Agents(Sergei V. Gulnik, Elena Afonina, and MichaelEissenstat).INDEX.