Basics of drug discovery in the biopharmaceutical industry
Historical landmarks in drug discovery and development
An overview of drug discovery and development in the twentieth century
Current status of drug discovery and development
The discovery-development interface
An overview of the problems facing the pharmaceutical industry

Introduction
Genome-based technologies for drug discovery
Role of genomics in drug discovery
Single nucleotide polymorphisms (SNPs)
SNPs in drug discovery
Technologies for genotyping
DNA sequencing
Restriction fragment length polymorphism
Amplification of refractory mutation system
CMSTs for detection of SNPs
Single base extension-tag array
SNP Consortium
Companies involved in SNP technologies for drug discovery
Gene expression profiling
Serial analysis of gene expression (SAGE)
Gene expression profiling system
Differential analysis of transcripts alternatively spliced (DATAS)
Antibody-based technologies for drug discovery
ProAb tissue profiling
ProxiMol
Subtractive antibody screening
Genetic surrogate for drug action
Screening in drug discovery
Cell-based screening system
Receptor targets: human versus animal tissues
AlphaScreen Technology
Tissue screening
High-throughput screening, automation and robotics
Detection technologies for HTS
Miniaturisation technologies in HTS
Automation of HTS
Automation in medicinal chemistry
Robotics
Companies involved in HTS
HTS for genes of unknown function
Combinatorial chemistry
Chemical libraries
Parallel synthesis
Split synthesis
Molecular diversity
Phage display
Purine libraries
PharmaCore combinatorial lead discovery library
Innovations in combinatorial chemistry
Combinatorial chemistry companies
Target validation technologies
Gene knockout technologies
Gene inactivation technologies
Animal models for genomics-based target validation methods
Inducible knockouts in mice
Role of knockout mice in drug discovery programmes
Antisense approaches to drug discovery
Antisense oligonucleotides for functional genomics and drug target validation
Triple helix oligonucleotides
Antisense oligonucleotides in a high-throughput approach for target validation
Antisense PNA for target validation
Aptamers
RNA as drug target
Ribozymes
Companies using antisense approaches to drug discovery
Biochips and microarrays for drug discovery
Finding lead compounds
High-throughput cDNA microarrays
Use of gene expression data to find new drug targets
Investigation of the mechanism of drug action
Companies using biochip technology for drug discovery

Introduction
Protein-expression mapping
Protein-complex identification
Role of 3-D structure of protein in drug discovery Random activation of gene expression (RAGE)
CD-Tagging
Proteomic approach to target identification and validation
Application of mass spectrometry for target identification
Structure-based drug design
Gene knockout and gene suppression for validating protein targets
Laser-mediated protein knockout for target validation
Integrated proteomics for drug discovery
Ligand-receptor binding
High-throughput proteomics
Target discovery and validation through protein interaction studies
Protein-protein interactions online
Protein-protein interaction analysis
Two-hybrid protein interaction technology
Protein arrays for lead optimisation
Biosensors for detection of small molecule-protein interactions
Inhibition of protein-protein interactions
Selective disruption of proteins by small molecules
From protein-protein interaction to a high throughput assay
Post-genomic combinatorial biology approach
Expression proteomics: protein level quantification
Identification of protein kinases
Analysis of post-translational modification of proteins by mass spectrometry
Transcription-aided drug design
Combination of RNA and protein profiling
Protein chip technology for drug discovery
Companies using proteomic technologies for drug discovery

Introduction
In silico biology
In silico search of drug targets by Biopendium
Combination of in silico and in vitro studies
Using in silico metabolism in the early drug discovery process
Bioinformatics for integrating genomics/proteomics in drug discovery
Protein structural database approach to drug design
Integration of bioinformatics in antibiotic research
Bioinformatic approach to prediction of drug safety in the discovery phase
Optimisation of selection of drug candidates through bioinformatics
Data mining
Bioinformatic companies involved in drug discovery

Pharmacogenesis
Role of model organisms
Role of C. elegans in drug discovery
Role of developmental biology in drug development
Role of evolutionary biology in drug discovery
Chemical genomics or chemogenomic approach to drug discovery
Automated ligand identification system
Chemoinformatics
Hybrid nuclear magnetic resonance techniques Virtual drug development

Introduction
Strategies for improving drug discovery in the post-genomic era
Role of combinatorial chemistry in the post-genomic drug discovery
Integration of genomics and proteomics for drug discovery
Pharmacogenetics and pharmacogenomics
Commercially relevant drug targets
Signal transduction as a drug discovery platform
Apoptosis as a signal transduction disorder
Cell signalling pathways as drug targets
GPCRs as drug targets
Caspase inhibitors
Companies with programmes in signal transduction-based drug discovery
Future prospects in cell transduction research
Ion channels as drug targets
Small molecules
Peptide therapeutics
Bacterial genomics and antimicrobial targets
Drug targets in cancer
Discovering drugs from unexplored natural resources
Selection of plant extracts for further study
High-throughput screening of compounds from natural sources
Improvements in lead generation
Improvement of lead validation systems
Pharmacokinetics and ADME
Preclinical toxicology
The role of toxicogenomics in drug discovery
Toxicoproteomics
Prediction of metabolic drug interactions
Integration of drug discovery and development
Decision-making for advancing a lead compound to a clinical candidate
Integration of drug delivery considerations in drug discovery process
Role of collaborations in drug discovery
Drivers for collaborative research
Strategic considerations for collaborations
Outsourcing discovery collaborations
Effective management of drug discovery technologies
Impact of the Internet on the R&D process
Drug discovery in relation to healthcare in the post-genomic era

Introduction
Markets for drug discovery technologies
Unfulfilled needs in drug discovery technologies
Market development opportunities
Potential of genome-based drug development
Outsourcing of drug development projects
Coping with rising costs of R&D
Risk reduction of termination of NCE
Patenting research tools for drug discovery

Introduction
Company Profiles
3-Dimensional Pharmaceuticals Inc.
Abbott Laboratories
Abgenix Inc.
ACADIA Pharmaceuticals Inc.
Advanced Bioanalytical Services
Affymax Research Institute
Althexis Company Inc.
Amgen
AMRAD Corporation Ltd
Anadys Pharmaceuticals Inc.
Applied Biosystems
Arena Pharmaceuticals
Argonex Discovery
ArQule Inc.
Array BioPharma Inc.
ARTEMIS Pharmaceuticals GmbH
Astex Technology Ltd
AstraZeneca Pharmaceuticals
Athersys
Atugen AG
Aurora Biosciences Corporation
Aventis Pharmaceutical Inc.
Axiom Biotechnologies Inc.
Axys Pharmaceuticals Inc.
Bayer AG
Biacore International AB
BioSignal Packard Inc.
Boehringer Ingelheim GmbH
Bristol-Myers Squibb Company
Cambridge Drug Discovery Ltd
Celera Genomics
Celgene Corporation
Cellomics Inc.
Celltech Chiroscience Ltd
Cellular Genomics Inc.
Cetek Corporation
ChemBridge Corporation
Chiron Corporation
CombiMatrix Corporation
Cubist Pharmaceuticals
Curis Inc.
De Novo Pharmaceuticals Ltd
Deltagen Inc.
DGI BioTechnologies
DiscoveRx Corporation
Discovery Partners International Inc.
Discovery Technologies Ltd
Diversa Corporation
Drug Discovery Ltd
Ecopia BioSciences Inc.
Entelos Inc.
EVOTEC BioSystems GmbH
Exelixis Inc.
ExonHit Therapeutics SA
Gemini Genomics (UK) Ltd
Gene Logic Inc.
Genome Therapeutics Corporation
Genzyme Molecular Oncology
Glaxo Wellcome
Graffinity Pharmaceutical Design GmbH
Hoffmann-La Roche Ltd
Human Genome Sciences Inc.
ICAgen Inc.
Iconix Pharmaceuticals
Inpharmatica Ltd
IRORI
Johnson Pharmaceutical Research Institute
Karo Bio AB
Lexicon Genetics Inc.
Ligand Pharmaceuticals Inc.
LION Biosciences AG
Lynx Therapeutics Inc.
MediChem
MEMOREC Stoffel GmbH
Merck & Co. Inc.
Millennium Pharmaceuticals Inc.
Molecular Devices Corporation
Molecular Mining Corporation
Molecular Simulations Inc.
MorphoSys AG
NeoGenesis Inc.
Neurogen Corporation
Novartis Pharma AG
Ontogen Corporation
OSI Pharmaceuticals Inc.
Oxford Glycosciences
Pfizer Pharmaceutical Group
Pharmacia Corporation
Pharmacopeia
Pharmagene plc
PPD Discovery
Proteus SA
Protherics plc
Rigel Pharmaceuticals Inc.
Roche Bioscience
Rosetta Inpharmatics Inc.
Schering-Plough Corporation
Serono Pharmaceutical Research Institute
SignalGene
SmithKline Beecham
Spotfire Inc.
Sumitomo Pharmaceuticals Co. Ltd.
Synaptic Pharmaceutical Corporation
Trega Biosciences
Vertex Pharmaceuticals Inc.
Xenon Genetics Inc.
Glossary Of Terms
Bibliography
List Of Abbreviations

Table 1.1: Landmarks in the discovery of modern medicine
Table 2.1: Companies involved in SNP technologies for drug discovery
Table 2.2: Some companies with HTS systems
Table 2.3: Collaborations between pharmaceutical and combinatorial chemistry companies
Table 2.4: Selected antisense companies and their approaches to drug discovery
Table 2.5: Selected companies using biochips and microarrays for drug discovery
Table 3.1: Selected companies using proteomic technologies for drug discovery
Table 4.1: Selected companies with novel bioinformatics and data management tools for ADME and toxicology
Table 4.2: Selected bioinformatic companies involved in drug discovery
Table 5.1: Companies following a developmental biology approach to functional genomics
Table 5.2: Selected companies with chemoinformatic technologies
Table 6.1: Selected companies involved in signal transduction-based drug discovery
Table 6.2: Selected companies involved in developing small molecule drugs
Table 6.3: Selected anticancer drug targets
Table 6.4: Companies involved in high-throughput screening of compounds from natural sources
Table 6.5: Selected lead validation screening systems
Table 7.1: Markets for drug discovery technologies

Figure 1.1: The drug discovery process
Figure 2.1: The role of genomics technologies in drug discovery
Figure 4.1: From bacterial genomes to potential drug targets: combination of in silico and gene knockout experiments
Figure 4.2: Role of bioinformatics in integrating genomics and proteomics in drug discovery
Figure 5.1: Chemical genomics approach to drug discovery
Figure 6.1: Distribution of approximately 1,000 drug targets for drugs currently available or in clinical development for various therapeutic areas
Figure 6.2: Procedure for selection of plant extracts for study
Figure 6.3: Technologies for optimising the R&D process
Figure 7.1: Unfulfilled needs in drug discovery technologies