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Optimization in Drug Discovery: In Vitro Methods de Gary W. Caldwell

Optimization in Drug Discovery: In Vitro Methods: Methods in Pharmacology and Toxicology

Editat de Gary W. Caldwell, Zhengyin Yan
en Limba Engleză Paperback – 23 aug 2016
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.
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Specificații

ISBN-13: 9781493960705
ISBN-10: 1493960709
Pagini: 614
Ilustrații: XVII, 597 p. 113 illus., 49 illus. in color.
Dimensiuni: 178 x 254 x 31 mm
Greutate: 0.85 kg
Ediția:Softcover reprint of the original 2nd ed. 2014
Editura: Humana Press Inc.
Colecția Humana
Seria Methods in Pharmacology and Toxicology

Locul publicării:Totowa, NJ, United States

Cuprins

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 Upan 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.

Textul de pe ultima copertă

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.

Caracteristici

Provides updated variations on assays as well as numerous new protocols for drug discovery optimization Features readily reproducible methods and protocols that are lab-tested and successful Includes expert tips and key implementation advice

Recenzii

"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