Optimization in Drug Discovery: In Vitro Methods

1. Small Molecule Formulation Screening Strategies in Drug Discovery
2. Assessment of Drug Plasma Protein Binding in Drug Discovery
3. Drug Partition in Red Blood Cells
4. Permeability Assessment Using 5-day Cultured Caco-2 Cell Monolayers
5. In Situ Single Pass Perfused Rat Intestinal Model
6. Metabolic Stability Assessed by Liver Microsomes and Hepatocytes
7. Metabolic Assessment in Alamethicin-Activated Liver Microsomes: Co-activating CYPs and UGTs
8. Phenotyping UDP-Glucuronosyltransferases (UGTs) Involved in Human Drug Metabolism: An Update
9. In Vitro CYP/FMO Reaction Phenotyping
10. Human Pregnane X Receptor (hPXR) Activation Assay in Stable Cell Lines
11. Characterization of Constitutive Androstane Receptor (CAR) Activation
12. DNA Binding (Gel Retardation Assay) Analysis for Identifi cation of Aryl Hydrocarbon (Ah) Receptor Agonists and Antagonists
13. Metabolite Identifi cation in Drug Discovery
14. Drug, Lipid, and Acylcarnitine Profi ling Using Dried Blood Spot (DBS) Technology in Drug Discovery
15. In Vitro Trapping and Screening of Reactive Metabolites Using Liquid Chromatography-Mass Spectrometry
16. Quantitative Assessment of Reactive Metabolites
17. In Vitro Assessment of the Reactivity of Acyl Glucuronides
18. Methods for Using the Mouse Lymphoma Assay to Screen for Chemical Mutagenicity and Photo-Mutagenicity

Thoroughly revised and updated, Optimization in Drug Discovery: In Vitro Methods, Second Editionpresents a wide spectrum of in vitro assays including formulation, plasma binding, absorption and permeability, cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) metabolism, CYP inhibition and induction, drug transporters, drug-drug interactions via assessment of reactive metabolites, genotoxicity, and chemical and photo-mutagenicity assays. Written for the Methods in Pharmacology and Toxicology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Expert authors have developed and utilized these in vitro assays to achieve “drug-like” characteristics in addition to efficacy properties and good safety profiles of drug candidates. Comprehensive and up-to-date, Optimization in Drug Discovery: In Vitro Methods, Second Edition aims to guide researchers down the difficult path to successful drug discovery and development.