Yan / Caldwell | Optimization in Drug Discovery | Buch | sack.de

Yan / Caldwell Optimization in Drug Discovery

In Vitro Methods

2004, 420 Seiten, Gebunden, Book, Format (B × H): 152 mm x 229 mm, Gewicht: 1 g Reihe: Methods in Pharmacology and Toxicology
ISBN: 978-1-58829-332-9
Verlag: Springer, Berlin

Yan / Caldwell Optimization in Drug Discovery

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e., hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.



Weitere Infos & Material

pKa, Solubility and Lipophilicity: Assessing Physicochemical Properties of Lead Compounds
Yushen Guo and Hong Shen
Use of Caco-2 Cell Monolayers to Study Drug Absorption and Metabolism
Ming Hu, Jie Ling, Huimin Lin, and Jun Chen
Absorption Screening Using the PAMPA Approach
Jeffrey A. Ruell and Alex Avdeef
In Situ Single-Pass Perfused Rat Intestinal Model for Absorption and Metabolism
Eun Ju Jeong, Yan Liu, Huimin Lin, and Ming Hu
In Vitro Permeation Study With Bovine Brain Microvessel Endothelial Cells
Seong-Hee Park, Sung-Hack Lee, Yaming Su, and Patrick J. Sinko
An Enzymatic Microplate Assay for Testing P-Glycoprotein Substrates and Inhibitors
S. Orlowski, J. Nugier, and Eric Ezan
Evaluation of Drug-Transporter Interactions Using In Vitro Cell Models
Yaming Su and Patrick J. Sinko
Plasma Protein-Binding Methods in Drug Discovery
Lucinda H. Cohen
Isothermal Titration Calorimetry Characterization of Drug-Binding Energetics to Blood Proteins
Gary W. Caldwell and Zhengyin Yan
Metabolic Stability Assessed by Liver Microsomes and Hepatocytes
David C. Ackley, Kevin T. Rockich, and Timothy R. Baker
In Vitro Drug Metabolite Profiling Using Hepatic S9 and Human Liver Microsomes
Wu-Nan Wu and Linda A. McKown
In Vitro Identification of UDP-glucuronosyltransferases Involved in Drug Metabolism
Michael H. Court
In Vitro CYP Induction in Human Hepatocytes
Daniel R. Mudra and Andrew Parkinson
High-Throughput Screening of Human Cytochrome P450 Inhibitors Using Fluorometric Substrates: Methodology for 25 Enzyme/Substrate Pairs
David M. Stresser
Evaluation of Cytochrome P450 Inhibition in Human Liver Microsomes
Zhengyin Yan and Gary W. Caldwell
Identification of CYP Mechanism-Based Inhibitors
Amin A. Nomeir, Jairam Palamanda, and Leonard Favreau
Detection of DNA Adducts by 32P-Postlabeling Analysis
Naomi Suzuki, Padmaja M. Prabhu, and Shinya Shibutani
Covalent DNA Adduct Formation Mediated by Cytochrome P450
Marie Stiborová
Application of In Vitro Comet Assay for Genotoxicity Testing
Bojana Zegura and Metka Filipic
Assessing DNA Damage Using a Reporter Gene System
Xuming Jia and Wei Xiao
Improvement of the Ames Test Using Human Liver S9 Preparation
Atsushi Hakura, Satoshi Suzuki, and Tetsuo Satoh
Screening for Chemical Mutagens Using the Mouse Lymphoma Assay
Tao Chen and Martha M. Moore
A High-Throughput Binding Assay for HERG
Keith Finlayson and John Sharkey
In Vitro Drug Metabolism: Thiol Conjugation
Wei Tang and Randy R. Miller
In Vitro Screening Assay of the Reactivity of Acyl Glucuronides
Sébastien Bolze


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