Cell-Based Assays for Drug Discovery

Published by: Trimark Publications

Published: Aug. 1, 2009 - 103 Pages

Table of Contents

1. Overview

1.1 Objectives of the Report

1.2 Methodology

1.3 Scope of the Report

1.4 Executive Summary

2. Technologies and Product Offering for High-Content Analysis

2.1 Definition of High-Content Analysis and Why it is so Attractive a Discipline

2.2 Classes of Measurements Possible with High-Content Analysis Approaches and Biological Functions Investigated

2.3 Instrumentation Platforms for High-Content Analysis

2.3.1 High-Content Screening Technology

2.4 Reagent and Assay Platforms for High-Content Analysis

2.5 Cell-based Screening Technologies in Drug Development

2.5.1 Applications of Cell-based Assays

2.5.2 Pharma Drug Discovery Paradigm and Compound Screening

2.5.3 High-Content Analysis in the Biopharmaceutical Industry

3. Market Analysis of the High-Content Tools Space

3.1 High-Content Analysis Market Size and Growth

3.2 Market Survey to Assess Qualitative and Quantitative Parameters of the High-Content Analysis Space

3.3 Experimental and Research Trends in High-Content Analysis

3.4 Challenges and Market Drivers in High-Content Analysis

3.4.1 Barriers to High-Content Analysis

3.4.2 Drivers of High-Content Analysis

3.5 High-Content Analysis in Combination with RNAi

3.6 Market Landscape of Instrumentation for High-Content Analysis

3.7 Reagent and Assay Usage in High-Content Analysis

3.8 Trends in the High-Content Analysis Assays/Reagents Space-Major Product Vendors

3.9 Emerging Market Trends in High-Content Analysis

3.10 Market Forecasts for the High-Content Analysis Space

3.11 Use of HCS in Pharmaceutical Companies

3.12 Qualitative Opportunities and Challenges for Market Adoption

4. Strategic Analysis of the High-Content Tools Space

4.1 Analysis of the High-Content Market Structure

4.2 Description of the Drug Discovery Marketplace and Definition of the Field

4.3 Key Market Drivers and Challenges in the High-Content Analysis Space

4.4 Consolidated Picture of the High-Content Analysis Marketplace

4.5 High-Content Analysis Market Sectors and Growth Rate

4.6 Vendors of High-Content Analysis Technology

5. High-Content Analysis Technology Platforms

5.1 Methods of Digital Imaging

5.2 Fluorescence Microscopy

5.3 Major High-Content Analysis Instrumentation

5.3.1 High-Content Analysis Platforms to Support GPCR Screening

5.4 High-Content Analysis Reagents

5.5 Imaging Software

5.6 Enterprise-Level IT Solutions to Support High-Content Screening Experiments

5.6.1 Image Analysis Algorithms

5.7 Use of RNAi in High-Content Analysis

5.8 Industry Alliances to Leverage RNAi and High-Content Analysis

5.9 Emerging Trends in High-Content Analysis Technology Platforms

6. High-Content Analysis in Drug Selection, Screening and Biomarker Discovery

6.1 Stem Cells as Tools for Drug Discovery

6.2 Cellular Systems Biology for Development of Toxicity Panels in Drug Safety Testing

6.3 Drug Discovery Companies Marketing Cell-based Assays

6.4 Companies Using Cell-based Assays in Drug Discovery Programs

6.4.1 Phenotypic Drug Discovery (PDD)

6.4.2 Application of Quantitative High-Throughput Screening to HCA Cell-based Assays

6.4.3 Application of High-Content Fingerprinting to Oncology Drug Discovery: Focus on in vitro and in vivo Phenocopying and Cancer Stem Cell Analysis

6.5 Target Discovery and Validation by RNAi Screening

6.6 FLIM-FRET Methodology

6.7 Multidimensional Fluorescence Imaging (MDFI) Technology

7. Company Profiles

7.1 Acumen Pharmaceuticals, Inc.

7.2 Acumen Bioscience (division of TTP Group)

7.3 Applied Biosystems

7.4 BD Biosciences

7.5 DiscoveRX

7.6 Evotec Technologies (acquired by PerkinElmer)

7.7 Fisher BioImage

7.8 General Electric, GE Healthcare

7.9 Guava Technologies (now a division of Millipore)

7.10 Integral Molecular (Akceli Inc.)

7.11 LemnaTech GmbH

7.12 Millipore

7.13 Molecular Devices Corporation, now a division of MDS Analytical Techniques

7.14 NIH Chemical Genomics Center

7.15 PerkinElmer

7.16 Sangamo Biosciences, Inc.

7.17 Spotfire (acquired by TIBCO)

7.18 Thermo Scientific Cellomics

7.19 Translational Genomics Research Institute

7.20 Vala Sciences, Inc.

8. Glossary of Terms in the High-Content Analysis Space

LIST OF FIGURES

Figure 2.1: Scope of Biological Parameters Addressed via a Typical High-Content Analysis Experiment

Figure 2.2: Classes of Assays in Life Science Research and Drug Discovery Illustrating the Relationship between Cell-based Assays and High-Content Analysis

Figure 2.3: New Paradigm for Drug Discovery and Development Illustrating the Central and Essential Role of Screening

Figure 2.4: Cumulative Known and New Drug Targets

Figure 3.1: Breakout of Market Survey Respondents by Geographical Location

Figure 3.2: Breakout of Market Survey Respondents by Affiliation-Academic, Commercial, Vendor

Figure 3.3: Segmentation of Respondent Pool Based upon Usage of High-Content Analysis in its Research Activities

Figure 3.4: Segmentation of the Survey Respondent Pool Based upon the Length of Time they have been Using High-Content Analysis in Their Research Activities

Figure 3.5: Number of Parameters Studied Simultaneously in High-Content Analysis Assays-Multivariate (Multi-Parameter) Analyses

Figure 3.6: Key Biological Processes Studied Utilizing High-Content Analysis Tools

Figure 3.7: Breakout of High-Content Analysis Assays Currently Performed or Expected to be Performed in the Future by Biological Pathway (or Target)

Figure 3.8: Breakout of High-Content Analysis Experiments Performed Per Week (Distributed in our Respondent Pool) Across the Various Biological Pathways (and Targets)

Figure 3.9: Which of the Biological Processes (Pathways/Targets) Addressed Using High-Content Analysis-based Approaches are Growing in Importance and which are Declining?

Figure 3.10: In Which Environment are High-Content Analysis Assays Performed-Primary Screen, Secondary Screen, ADME/Tox Screen?

Figure 3.11: Key Challenges Faced by the Research Community in its Practice of High-Content Analysis

Figure 3.12: Various Drivers Leading the Research Community to Perform High-Content Analysis

Figure 3.13: HCA with RNAi-Current and Future Experimental Formats

Figure 3.14: HCA with RNAi-Number of Experiments Performed Per Month by the Survey Respondent Pool

Figure 3.15: Growing and Steady Usage of Various Formats where RNAi is coupled with HCA

Figure 3.16: Penetration of the Different High-Content Analysis Instrumentation Platforms into the Marketplace

Figure 3.17: Instrumentation Platforms for High-Content Analysis Ranked by Top Choice and Second Tier

Figure 3.18: High-Content Analysis Instrumentation and where they Lie on the Throughput Curve

Figure 3.19: Top Instrumentation Value Drivers in the High-Content Analysis Space

Figure 3.20: Important Sub-Cellular Features Studied via High-Content Analysis Approaches

Figure 3.21: Breakout of End-Point Versus Kinetic Assays in the High-Content Analysis Space

Figure 3.22: Types of Cellular Targets Studied Using High-Content Analysis Approaches

Figure 3.23: Top-most Target Class Studied Utilizing High-Content Analysis Approaches

Figure 3.24: Distribution of High-Content Analysis Experiments across the Respondent Pool-Number of Experiments Performed Per Week

Figure 3.25: Average Reagent/Assay Costs Per High-Content Analysis Experiment

Figure 3.26: Stratification of Reagent/Assay Suppliers into the High-Content Analysis Space

Figure 3.27: Monthly Reagent/Assay Purchases for High-Content Analysis by the End-user Community from Various Vendors

Figure 3.28: Growth or Decline in Importance of the Various High-Content Analysis Vendors to the End-user Community

Figure 3.29: Percentage of High-Content Analysis Experiments that Involve GFP across the Market Landscape

Figure 3.30: Breakout of High-Content Analysis Reagents Marketplace: Made-in-House Versus Off-the-Shelf

Figure 3.31: Breakout of Spending on Various Components of the High-Content Analysis Discipline

Figure 3.32: Historic/Forecast Growth of the Total Screening Space, Broken-out by Primary Screening, Secondary Screening (including High-Content Analysis as a Subset) and ADME/Tox, for 2004-2010

Figure 3.33: Historic/Forecast Growth of the Screening Space-Broken-out by Cell-based Assays and Biochemical Assays, 2004-2010

Figure 4.1: Drug Discovery and Development Ensemble and the Position of the Various Segments of High-Content Analysis in the Space

Figure 4.2: Relative Size and Position of the High-Content Analysis Space in the Overall Scheme of the Life Science Tools Marketplace

Figure 5.1: High-Content Analysis-Positional Biosensors Using Caspases and Monitoring the Translocation of a Tagged Protein from the Cytoplasm to the Nucleus

Figure 6.1: HCA Target Classes: Breakout of Current Drug Targets into Their Constituent Classes

Figure 6.2: GPCR Assay Technologies

LIST OF TABLES

Table 2.1: Comparison of the Key Features of High-Content Analysis and High-Throughput Screening

Table 2.2: Impact of High-Content Analysis on Drug Discovery-Impact of Several Drivers

Table 2.3: Biological Application Areas Associated with High-Content Analysis

Table 2.4: Classes of Measurements and Targets Identified Using Phenotypic Screening (High-Content Analysis)

Table 2.5: Classes of Cellular Measurements Possible with Fluorescent Protein Biosensors

Table 2.6: Multi-Parameter High-Content Analysis Assays to Study Biological Systems in Life Science Research and Drug Discovery, Demonstrating the Breadth and Scalability of the High-Content Analysis Approach

Table 2.7: Companies Offering Systems for High-Throughput Imaging

Table 2.8: Comparison of the Major Instrumentation Platforms and Their Associated Specifications for High-Content Analysis-I

Table 2.9: Comparison of the Major Instrumentation Platforms and Their Associated Specifications for High-Content Analysis-II

Table 2.10: Price Points and Target Markets of the Various High-Content Analysis Instrument Platforms

Table 2.11: Companies Offering Flow Cytometry Products and Services

Table 2.12: Integrated Product Platforms Offered by the Different High-Content Analysis Vendors

Table 2.13: High-Content Analysis Assays Developed by Thermo Scientific Cellomics

Table 2.14: Thermo Scientific Cellomics HCS Reagent Kits (formerly called "HitKits") and Their Therapeutic Areas of Application

Table 2.15: Millipore's HCA Assay/Reagent Portfolio

Table 2.16: Cell Lines for GPCR High-Content Analysis that can be Deployed onto the BD Biosciences/Atto Pathway HT™ Instrument Platform

Table 2.17: Examples of High-Content Screens

Table 3.1: What Fraction of High-Content Analysis Assays are Cell-based Versus Biochemical-based

Table 4.1: Comparison of the Key Features of High-Content Analysis and High-Content Screening

Table 4.2: Snapshot of the Various HCA Assays, Demonstrating the Scalability of this Discipline

Table 5.1: Modes of Digital Imaging

Table 5.2: Modes of Fluorescence Microscopy

Table 5.3: Major High-Content Analysis Instrumentation

Table 5.4: Image Analysis Algorithms

Abstract

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