Enzyme Inhibition in Drug Discovery and Development (eBook)

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.

"The description of each topic is clear, well organized and
informative, making the book a useful or even essential high-level
handbook." (ChemMedChem, November 2010)