Optimization in Drug Discovery In Vitro Methods
Optimization in Drug Discovery In Vitro Methods
edited by Gary W. Caldwell, Zhengyin Yan.
- 2nd edition 2014
- 1 recurso en línea (XVII, 597 páginas) 113 ilustraciones, 49 ilustraciones a color
- Methods in Pharmacology and Toxicology 1940-6053 .
Small Molecule Formulation Screening Strategies in Drug Discovery -- Assessment of Drug Plasma Protein Binding in Drug Discovery -- Drug Partition in Red Blood Cells -- Permeability Assessment Using 5-Day Cultured Caco-2 Cell Monolayers -- In Situ Single Pass Perfused Rat Intestinal Model -- Metabolic Stability Assessed by Liver Microsomes and Hepatocytes -- Metabolic Assessment in Alamethicin-Activated Liver Microsomes: Co-Activating CYPs and UGTs -- Phenotyping UDP-Glucuronosyltransferases (UGTs) Involved in Human Drug Metabolism: An Update -- In Vitro CYP/FMO Reaction Phenotyping -- Human Pregnane X Receptor (hPXR) Activation Assay in Stable Cell Lines -- Characterization of Constitutive Androstane Receptor (CAR) Activation -- DNA Binding (Gel Retardation Assay) Analysis for Identification of Aryl Hydrocarbon (Ah) Receptor Agonists and Antagonists -- Cell-Based Assays for Identification of Aryl Hydrocarbon Receptor (AhR) Activators -- In Vitro CYP Induction Using Human Hepatocytes -- Assessment of CYP3A4 Time-Dependent Inhibition in Plated and Suspended Human Hepatocytes -- Evaluation of Time-Dependent CYP3A4 Inhibition Using Human Hepatocytes -- Rapidly Distinguishing Reversible and Time-Dependent CYP450 Inhibition Using Human Liver Microsomes, Co-Incubation, and Continuous Fluorometric Kinetic Analyses -- Identification of Time-Dependent CYP Inhibitors Using Human Liver Microsomes (HLM) -- CYP Time-Dependent Inhibition (TDI) Using an IC50 Shift Assay with Stable Isotopic Labeled Substrate Probes to Facilitate Liquid Chromatography/Mass Spectrometry Analyses -- Screening for P-Glycoprotein (Pgp) Substrates and Inhibitors -- In Vitro Characterization of Intestinal Transporter, Breast Cancer Resistance Protein (BCRP) -- In Vitro Characterization of Intestinal and Hepatic Transporters: MRP2 -- In Vitro Characterization of Hepatic Transporters OATP1B1 and OATP1B3 -- In Vitro Characterization of Renal Transporters OAT1, OAT3, and OCT2 -- General Guidelines for Setting Up an In Vitro LC/MS/MS Assay -- Metabolite Identification in Drug Discovery -- Drug, Lipid, and Acylcarnitine Profiling Using Dried Blood Spot (DBS) Technology in Drug Discovery -- In Vitro Trapping and Screening of Reactive Metabolites Using Liquid Chromatography-Mass Spectrometry -- Quantitative Assessment of Reactive Metabolites -- In Vitro Assessment of the Reactivity of Acyl Glucuronides -- In Vitro COMET Assay for Testing Genotoxicity of Chemicals -- Assessing DNA Damage Using a Reporter Gene System -- Improved AMES Test for Genotoxicity Assessment of Drugs: Preincubation Assay Using a Low Concentration of Dimethyl Sulfoxide -- 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 Edition presents 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.
9781627037426
10.1007/978-1-62703-742-6 doi
Small Molecule Formulation Screening Strategies in Drug Discovery -- Assessment of Drug Plasma Protein Binding in Drug Discovery -- Drug Partition in Red Blood Cells -- Permeability Assessment Using 5-Day Cultured Caco-2 Cell Monolayers -- In Situ Single Pass Perfused Rat Intestinal Model -- Metabolic Stability Assessed by Liver Microsomes and Hepatocytes -- Metabolic Assessment in Alamethicin-Activated Liver Microsomes: Co-Activating CYPs and UGTs -- Phenotyping UDP-Glucuronosyltransferases (UGTs) Involved in Human Drug Metabolism: An Update -- In Vitro CYP/FMO Reaction Phenotyping -- Human Pregnane X Receptor (hPXR) Activation Assay in Stable Cell Lines -- Characterization of Constitutive Androstane Receptor (CAR) Activation -- DNA Binding (Gel Retardation Assay) Analysis for Identification of Aryl Hydrocarbon (Ah) Receptor Agonists and Antagonists -- Cell-Based Assays for Identification of Aryl Hydrocarbon Receptor (AhR) Activators -- In Vitro CYP Induction Using Human Hepatocytes -- Assessment of CYP3A4 Time-Dependent Inhibition in Plated and Suspended Human Hepatocytes -- Evaluation of Time-Dependent CYP3A4 Inhibition Using Human Hepatocytes -- Rapidly Distinguishing Reversible and Time-Dependent CYP450 Inhibition Using Human Liver Microsomes, Co-Incubation, and Continuous Fluorometric Kinetic Analyses -- Identification of Time-Dependent CYP Inhibitors Using Human Liver Microsomes (HLM) -- CYP Time-Dependent Inhibition (TDI) Using an IC50 Shift Assay with Stable Isotopic Labeled Substrate Probes to Facilitate Liquid Chromatography/Mass Spectrometry Analyses -- Screening for P-Glycoprotein (Pgp) Substrates and Inhibitors -- In Vitro Characterization of Intestinal Transporter, Breast Cancer Resistance Protein (BCRP) -- In Vitro Characterization of Intestinal and Hepatic Transporters: MRP2 -- In Vitro Characterization of Hepatic Transporters OATP1B1 and OATP1B3 -- In Vitro Characterization of Renal Transporters OAT1, OAT3, and OCT2 -- General Guidelines for Setting Up an In Vitro LC/MS/MS Assay -- Metabolite Identification in Drug Discovery -- Drug, Lipid, and Acylcarnitine Profiling Using Dried Blood Spot (DBS) Technology in Drug Discovery -- In Vitro Trapping and Screening of Reactive Metabolites Using Liquid Chromatography-Mass Spectrometry -- Quantitative Assessment of Reactive Metabolites -- In Vitro Assessment of the Reactivity of Acyl Glucuronides -- In Vitro COMET Assay for Testing Genotoxicity of Chemicals -- Assessing DNA Damage Using a Reporter Gene System -- Improved AMES Test for Genotoxicity Assessment of Drugs: Preincubation Assay Using a Low Concentration of Dimethyl Sulfoxide -- 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 Edition presents 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.
9781627037426
10.1007/978-1-62703-742-6 doi