3.1 High Throughput Screening In Vitro and In Silico
3.2 Metabolizing Enzyme Systems for In Vitro Analysis
3.3 The Use of Expressed Recombinant Human
Enzymes
3.4 Automated In Vitro Enzyme Metabolizing Assays
3.5 Correlation between Enzyme Distribution in the Liver
and Their Importance in Drug Metabolism
3.6 Use of Metabolic Assays in Second-Generation Drug
Discovery
3.7 Induction of Drug Metabolizing Enzymes
3.8 Transient Transfection Assays to Study Ethanol
Metabolism
3.9 Computational Models of Drug Metabolism
3.10 Use of Metabolic Information in Drug Design
3.11 Computer Models to Predict Physicochemical
Compound Characteristics
3.12 Computer Models to Predict Substrate Specificity
3.13 The Future of Drug Discovery
3.14 Questions & Answers
4. Cytochrome P450 Assays for Miniaturized Formats and Library Screening
4.1 Introduction
4.2 Developing Fluorescent Substrates for Cytochrome
P450 Isozymes
4.3 Fluorescent Substrates for CYP3A4
4.4 Assay Validation by HPLC
4.5 Calculating Apparent Ki and IC50 Values
4.6 Fluorescent Substrates for CYP2D6
4.7 Fluorescent Substrates for CYP2C9
4.8 Conclusions
4.9 Questions & Answers
5. Drug-Drug Interactions: High Throughput Assays to Screen for Inhibition of Human Cytochromes P450
5.1 Post-Approval Issues with Drug Interactions
5.2 Determining the Need and Extent to Test for
Metabolic Interactions
5.3 Requirements for Developing High Throughput
Metabolic Assay Systems
5.4 Gentest's High Throughput Inhibition Assays
5.5 Cytochrome P450 Inhibition Screens Using
Fluorogenic Substrates
5.7 Identification of Mechanism-Based Inhibitors
5.8 Case Study: Prediction of Drug Interactions of
Posicor
5.9 Conclusions
5.10 Questions & Answers
6. Drug Disposition: Rapid Throughput Methods to Quantify Compound Solubility
6.1 Combining Bases of Knowledge to Optimize Drug
Discovery
6.2 Oral Absorption Problems
6.3 Structural Properties of Drug-Like Compounds
6.4 Other Properties of Drug-Like Compounds
6.5 Developing Good Drug Candidates
6.6 Rationale for Turbidimetric Assays in Drug Discovery
6.7 Pfizer's Flow Cell Assay and Equipment
6.8 Pfizer's Plate Reader Assay and Equipment
6.9 System Integration of Tubidimetric Assays
6.10 Reproducibility and Correlation of Turbidimetric
Assays with Other Data
6.11 Predicting Poor Solubility
7. Screening Compounds for Oral Absorption Using High Throughput Cellular Assays
7.1 Introduction
7.2 The Use of Caco2 Cell Culture Assays in Drug
Screening
7.3 The Cell Automation System
7.4 Correlation between In Vitro Permeation Values and
Absorption in Humans
7.5 Applications of High Throughput Caco2 Cell Assays
7.6 Case Study: The Selection of a Lead Compound from
a Series of HNE Inhibitors
7.7 Conclusion
8. Screening Compounds for CNS Permeability using Blood Brain Barrier Models
8.1 Introduction
8.2 Anatomy of the Blood Brain Barrier
8.3 Anatomy of the Blood CSF Barrier
8.4 The Metabolic Barrier
8.5 The CNS Penetration Team at Glaxo Wellcome
8.6 In Vivo and In Vitro Approaches to Study CNS
Permeation
8.7 Determining the Mechanism of Brain Penetration for
an Anti-HIV Drug
8.8 An Alternative In Vitro Model for Brain Permeation
8.9 Validation of the MDCK Cell Culture Model
8.10 Relevance of Early Stage In Vitro Models to In Vivo
Brain Permeation
8.11 Application of the In Vitro Model in a Drug
Discovery Project
8.12 Computational Models
8.13 Integrating Permeation Screens for CNS
Compounds
8.14 Summary
8.15 Questions & Answers
9. Pharmacogenomics Impact on Early Lead Selection
9.1 Introduction
9.2 Transcriptional and Proteomic Profiling
9.3 Creating a Proteomic Database
9.4 Use of Proteomics to Accelerate Targeted Drug
Discovery
9.5 The Role of Transcriptional Analysis in Oncogenesis
EGF-Induced Differential Gene Expression in Tumor
Cells
9.6 The Role of Gene Expression Studies in Studying
Drug-Target Interactions
9.7 Anti-Fungal Drugs and Sterol Biosynthesis
Construction of Proteome Databases
9.8 Steroids and the Anti-Inflammatory Response
Molecular Dissection of the Human Inflammatory
Response
9.9 Transcription Profiling for Toxicology Testing
9.10 Looking Forward
9.11 Questions & Answers
Pricing:
All 3 Volumes - $2,490
Volume 1 - High Throughput Screening Assays- $1,290
Volume 2 - In Silico Biology - $1,290
Volume 3 - Early Compound Attrition - $1,290
