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Biomedical Sciences - Pharmacology & Toxicology | Optimization in Drug Discovery - In Vitro Methods

Optimization in Drug Discovery

In Vitro Methods

Caldwell, Gary W., Yan, Zhengyin (Eds.)

2nd ed. 2014, XVII, 597 p. 113 illus., 49 illus. in color.

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  • 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

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.

Content Level » Professional/practitioner

Keywords » Biopharmaceutics - Drug candidates - In vitro and in situ assays - Pharmacodynamic - Pharmacokinetics - Toxicokinetics

Related subjects » Pharmacology & Toxicology

Table of contents 

1. Small Molecule Formulation Screening Strategies in Drug Discovery

            Gary W. Caldwell, Becki Hasting, John Masucci, and Zhengyin Yan


2. Assessment of Drug Plasma Protein Binding in Drug Discovery

            Dennis Kalamaridis and Nayan Patel


3. Drug Partition in Red Blood Cells

            Dennis Kalamaridis and Karen DiLoreto


4. Permeability Assessment Using 5-Day Cultured Caco-2 Cell Monolayers

            Gary W. Caldwell, Chrissa Ferguson, Robyn Buerger, Lovonia Kulp, and Zhengyin Yan


5. In Situ Single Pass Perfused Rat Intestinal Model

            Maria Markowska and L. Mark Kao


6. Metabolic Stability Assessed by Liver Microsomes and Hepatocytes

            Kevin J. Coe and Tatiana Koudriakova


7. Metabolic Assessment in Alamethicin-Activated Liver Microsomes: Co-Activating CYPs and UGTs

            Gary W. Caldwell and Zhengyin Yan


8. Phenotyping UDP-Glucuronosyltransferases (UGTs) Involved in Human Drug Metabolism: An Update

            Michael H. Court


9. In Vitro CYP/FMO Reaction Phenotyping

            Carlo Sensenhauser


10. Human Pregnane X Receptor (hPXR) Activation Assay in Stable Cell Lines

            Judy L. Raucy


11. Characterization of Constitutive Androstane Receptor (CAR) Activation

            Caitlin Lynch, Haishan Li, and Hongbing Wang


12. DNA Binding (Gel Retardation Assay) Analysis for Identification of Aryl Hydrocarbon (Ah) Receptor Agonists and Antagonists

            Anatoly A. Soshilov and Michael S. Denison


13. Cell-Based Assays for Identification of Aryl Hydrocarbon Receptor (AhR) Activators

            Guochun He, Jing Zhao, Jennifer C. Brennan, Alessandra A. Affatato, Bin Zhao, Robert H. Rice, and Michael S. Denison


14. In Vitro CYP Induction Using Human Hepatocytes

            Monica Singer, Carlo Sensenhauser, and Shannon Dallas


15. Assessment of CYP3A4 Time-Dependent Inhibition in Plated and Suspended Human Hepatocytes

            J. George Zhang and David M. Stresser


16. Evaluation of Time-Dependent CYP3A4 Inhibition Using Human Hepatocytes

            Yuan Chen and Adrian J. Fretland


17. Rapidly Distinguishing Reversible and Time-Dependent CYP450 Inhibition Using Human Liver Microsomes, Co-Incubation, and Continuous Fluorometric Kinetic Analyses

            Gary W. Caldwell and Zhengyin Yan


18. Identification of Time-Dependent CYP Inhibitors Using Human Liver Microsomes (HLM)

            Kevin J. Coe, Judith Skaptason, and Tatiana Koudriakova


19. CYP Time-Dependent Inhibition (TDI) Using an IC50 Shift Assay with Stable Isotopic Labeled Substrate Probes to Facilitate Liquid Chromatography/Mass Spectrometry Analyses

            Gary W. Caldwell and Zhengyin Yan


20. Screening for P-Glycoprotein (Pgp) Substrates and Inhibitors

            Qing Wang and Tina M. Sauerwald


21. In Vitro Characterization of Intestinal Transporter, Breast Cancer Resistance Protein (BCRP)

            Chris Bode and Li-Bin Li


22. In Vitro Characterization of Intestinal and Hepatic Transporters: MRP2

            Ravindra Varma Alluri, Peter Ward, Jeevan Kunta, Brian C. Ferslew, Dhiren R. Thakker, and Shannon Dallas


23. In Vitro Characterization of Hepatic Transporters OATP1B1 and OATP1B3

            Blair Miezeiewski and Allison McLaughlin


24. In Vitro Characterization of Renal Transporters OAT1, OAT3, and OCT2

            Ying Wang and Nicole Behler


25. General Guidelines for Setting Up an In Vitro LC/MS/MS Assay

            John A. Masucci and Gary W. Caldwell


26. Metabolite Identification in Drug Discovery

            Wing W. Lam, Jie Chen, Rongfang Fran Xu, Jose Silva, and Heng-Keang Lim


27. Drug, Lipid, and Acylcarnitine Profiling Using Dried Blood Spot (DBS) Technology in Drug Discovery

            Wensheng Lang, Jenson Qi, and Gary W. Caldwell


28. In Vitro Trapping and Screening of Reactive Metabolites Using Liquid Chromatography-Mass Spectrometry

            Zhengyin Yan and Gary W. Caldwell


29. Quantitative Assessment of Reactive Metabolites

            Jie Chen, Rongfang Fran Xu, Wing W. Lam, Jose Silva, and Heng Keang Lim


30. In Vitro Assessment of the Reactivity of Acyl Glucuronides

            Rongfang Fran Xu, Wing W. Lam, Jie Chen, Michael McMillian, Jose Silva, and Heng Keang Lim


31. In Vitro COMET Assay for Testing Genotoxicity of Chemicals

            Haixia Lin, Nan Mei, and Mugimane G. Manjanatha


32. Assessing DNA Damage Using a Reporter Gene System

            Michael Biss and Wei Xiao


33. Improved AMES Test for Genotoxicity Assessment of Drugs: Preincubation Assay Using a Low Concentration of Dimethyl Sulfoxide

            Atsushi Hakura


34. Methods for Using the Mouse Lymphoma Assay to Screen for Chemical Mutagenicity and Photo-Mutagenicity

            Nan Mei, Xiaoqing Guo, and Martha M. Moore

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