Optimization in Drug Discovery
Optimization in Drug Discovery
edited by Zhengyin Yan, Gary W. Caldwell.
- 1st edition 2004
- 1 recurso en línea (XVI, 420 páginas)
- Methods in Pharmacology and Toxicology 1940-6053 .
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.
Although parallel synthesis combined with high-throughput screening has made it easier to generate highly potent drug candidates, many of these compounds never make the grade because they either prove to be unsafe or lack the necessary physicochemical and pharmacokinetic properties. In Optimization in Drug Discovery: In Vitro Methods, a panel of researchers and experts from leading universities and major pharmaceutical companies from all over the world provide proven solutions to this expensive problem with a collection of cutting-edge experimental protocols for early in vitro evaluation of new chemical entities (NCE). These readily reproducible assays measure such critical parameters as physicochemical properties, adsorption, plasma binding, metabolism, drug interactions, and toxicity. All protocols follow the successful Methods in Molecular Biology™ series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and highly practical, Optimization in Drug Discovery: In Vitro Methods systematically collects and describes the key methods for uncovering-as early in the discovery stage as possible-those defects that can eliminate candidate drugs from preclinical and clinical development.
9781592598007
10.1385/1592598005 doi
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.
Although parallel synthesis combined with high-throughput screening has made it easier to generate highly potent drug candidates, many of these compounds never make the grade because they either prove to be unsafe or lack the necessary physicochemical and pharmacokinetic properties. In Optimization in Drug Discovery: In Vitro Methods, a panel of researchers and experts from leading universities and major pharmaceutical companies from all over the world provide proven solutions to this expensive problem with a collection of cutting-edge experimental protocols for early in vitro evaluation of new chemical entities (NCE). These readily reproducible assays measure such critical parameters as physicochemical properties, adsorption, plasma binding, metabolism, drug interactions, and toxicity. All protocols follow the successful Methods in Molecular Biology™ series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and highly practical, Optimization in Drug Discovery: In Vitro Methods systematically collects and describes the key methods for uncovering-as early in the discovery stage as possible-those defects that can eliminate candidate drugs from preclinical and clinical development.
9781592598007
10.1385/1592598005 doi