Optimization in Drug Discovery

• pKa, Solubility, and Lipophilicity.- Use of Caco-2 Cell Monolayers to Study Drug Absorption and Metabolism.- Absorption Screening Using the PAMPA Approach.- In Situ Single-Pass Perfused Rat Intestinal Model for Absorption and Metabolism.- In Vitro Permeation Study With Bovine Brain Microvessel Endothelial Cells.- An Enzymatic Microplate Assay for Testing P-Glycoprotein Substrates and Inhibitors.- Evaluation of Drug-Transporter Interactions Using In Vitro Cell Models.- Plasma Protein-Binding Methods in Drug Discovery.- Isothermal Titration Calorimetry Characterization of Drug-Binding Energetics to Blood Proteins.- Metabolic Stability Assessed by Liver Microsomes and Hepatocytes.- In Vitro Drug Metabolite Profiling Using Hepatic S9 and Human Liver Microsomes.- In Vitro Identification of UDP-Glucuronosyltransferases (UGTs) Involved in Drug Metabolism.- In Vitro CYP Induction in Human Hepatocytes.- High-Throughput Screening of Human Cytochrome P450 Inhibitors Using Fluorometric Substrates.- Evaluation of Cytochrome P450 Inhibition in Human Liver Microsomes.- Identification of CYP Mechanism-Based Inhibitors.- Detection of DNA Adducts by 32P-Postlabeling Analysis.- Covalent DNA Adduct Formation Mediated by Cytochrome P450.- Application of In Vitro Comet Assay for Genotoxicity Testing.- Assessing DNA Damage Using a Reporter Gene System.- Improvement of the Ames Test Using Human Liver S9 Preparation.- Screening for Chemical Mutagens Using the Mouse Lymphoma Assay.- A High-Throughput Binding Assay for HERG.- In Vitro Drug Metabolism.- In Vitro Screening Assay of the Reactivity of Acyl Glucuronides.

"This book covers most of the currently used techniques in lead optimization with respect to ADME and safety profiles...would be very useful addition to the library of any drug scientist interested in an introduction to these important methods. Each chapter treats its topic in a concise manner and provides ample references to lead the reader to more detailed information."-Doody's Health Sciences Book Review Journal "...very useful technically...invaluable to those changing roles or joining a pharmaceutical company, it is also very helpful for scientists in the biotech industry who are new to drug discovery." - Immunology News "The book provides a wealth of relevant information...the tome is neatly designed, well constructed and easy to read." - ISSX Newsletter "...a useful reference handbook for in vitro ADMET assays." - ChemBioChem