Reportlinker Adds Preclinical Models: Innovative Solutions to Accelerate Drug Discovery and Development

Friday, April 2, 2010 Research News
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NEW YORK, April 1 announces that a new market research report is available in its catalogue:

Preclinical Models: Innovative solutions to accelerate drug discovery and development

Preclinical models are developed to test lead compounds for toxicity and efficacy. They are valuable tools to minimize development costs and reduce failures prior to commencement of human trials. Problems with traditional animal models such as cost, ethics, and suitability has prompted researchers to develop new models and systems to overcome such disadvantages. Alternative approaches include new vertebrate, nonvertebrate, computer-based and imaging models that offer new perspectives and utility to aid the drug discovery and development process.

This report explores novel preclinical models that show promise to expedite and improve the target validation and lead optimization timeline and discusses the various advantages and disadvantages of ADMET screening technologies to provide insight on which models or systems may enhance the R&D function of pharmaceutical and biotechnology organisations.

Additionally, the report provides an outlook for preclinical testing over the next decade and how pharmaceutical companies may need to adjust to new systems and models to improve their efficiencies. It uniquely focuses on more than 60 companies that are involved in using or developing ADMET technologies to advance preclinical research and provides an update on recent company activities and developments where new models and systems are employed to accelerate the discovery and development process.

Key features of this report

Scope of this report

Key Market Issues

Key findings from this report

Key questions answered

1. What are preclinical models and how are they important to the pharmaceutical industry?

2. What are the advantages and disadvantages of preclinical models in ADMET screening?

3. What are the innovations in preclinical models?

4. What are the trends in preclinical research?

5. How are in-vivo, in-vitro, in-silico and systems biology models being developed for ADMET?

6. How are companies building ADMET capabilities?

Companies mentioned

Ariadne Genomics , GeneGo , Genomatix , Genstruct , Ingenuity Systems , Merrimack Pharmaceuticals , Physiomics , Accelrys , Advanced Chemistry Development , Aureus Pharma , Chemical Computing Group , Entelos , Gene Network Sciences , Leadscope , Life Technologies Corporation , Molecular Discovery , Molecular Networks , Noray Bioinformatics , Schrodinger , Simcyp , Simulations Plus , TerraBase , Tripos , , , , , , , , , ,

Table of Contents

Preclinical models

Executive summary 10

Preclinical models in drug discovery and development 10

In vivo models in preclinical research 11

In vitro models in preclinical research 12

In silico models in preclinical research 13

Systems biology models in drug discovery 14

Chapter 1 Preclinical models in drug discovery and development 16

Summary 16

Introduction: importance of preclinical models for toxicity screening in drug development 17

Preclinical ADMET testing systems 17

The challenge: reducing drug attrition rates in preclinical screening 19

Importance of ADMET screening 22

Applying of ADMET to the drug discovery and development process 22

Importance of in vivo models 23

Established in vivo and in vitro ADMET tools to screen compounds 25

Toxicity and genotoxicity screening 26

Predicting toxicity with paracellular markers 27

In vitro ADMET screening in preclinical drug development 27

Advantages and disadvantages of conventional ADME screening tools in preclinical drug development 28

Oral absorption prediction 28

Metabolism prediction 29

In vivo ADMET animal models 30

Established ADMET study methods in animal models 32

Radiolabels 32

Cassette dosing 32

Semi-simultaneous dosing 33

Conclusion 34

Limitations of traditional in vitro and in vivo ADMET screening methods 34

New approaches to predict ADMET in preclinical development 36

Metabolomics 36

Advantages of metabolomics in drug discovery and development 37

Lead prioritization using metabolomics 37

Metabolomics and ADMET studies 37

Strengths and limitations of metabolomics for preclinical research 38

Metabolomics and "systems biology" - a unified approach to preclinical

ADMET screening 40

Company focus: Merrimack Pharmaceuticals 41

Other emergent technologies used in preclinical drug discovery and development 42

Nanotechnologies in preclinical studies 42

Novel imaging systems 43

Preclinical research and recent multinational pharmaceutical company activities 44

Bayer AG and Nimbus Biotechnology 44

Pfizer/Johnson and Johnson and WuXi Pharma Tech 44

Roche 44

Sanofi-Aventis 45

UCB Pharma 45

Chapter 2 In vivo models in preclinical research 48

Summary 48

Vertebrate animal models in preclinical discovery and development 49

Assessment of predictive value of animal models 49

Rodent models 50

The need for improved small animal models 50

Humanized rodent models 51

Advantages and disadvantages of zebrafish models in preclinical research 52

Recent progress with vertebrate models 54

ADMET screens and zebrafish models: company developments and technologies 54

Discovery Genomics 54

Evotec AG 55

Phylonix 56

Summit 56

ZF Biolabs 57

Zygogen 58

ADMET screens in rodent models: selected company developments and technologies 59

Lexicon Pharmaceuticals 59

Taconic 59

Xenogen's (now part of Caliper) 61

Sigma-Aldrich 62

Invertebrate animal models in preclinical discovery and development 63

Drosophila melanogaster (fruit fly) 63

Aktogen 64

En Vivo Pharmaceuticals 66

Exelixis 67

Medros Pharmaceuticals 67

Caenorhadbitis elegans (nematode) 68

Novel in vivo/ex-vivo focus: Locusta migratoria (locust) 68

Chapter 3 In vitro models in preclinical research 72

Summary 72

Importance of in vitro models in preclinical toxicity testing 73

In vitro technologies for drug discovery and development 74

Recent company developments 74

Affymetrix 74

Beckman Coulter 75

Covance 75

Gene Logic 75

HemoGenix 76

Recent developments in drug transport and metabolism 76

Qualyst 76

Xenobiotic Laboratories 77

Progress in cell-based in vitro assays 77

Use of cultured cells for ADMET studies in preclinical research 77

In vitro distribution 80

In vitro solubility 80

In vitro ADMET assays and cell-type selection 81

Recent developments in cell-based platforms for preclinical drug screening 83

Cell-based assays and liver toxicity 83

Stem cells in drug discovery and development 84

Stem cells and ADMET in drug discovery and development 85

Novel in vitro technologies in preclinical research 87

Nanotechnologies and ADMET in drug discovery and development 87

Chapter 4 In silico models in preclinical research 92

Summary 92

In silico models in drug discovery and development 93

Molecular modeling in silico 94

Computer models to predict ADMET 95

Methodological approaches to in silico models 95

Recent commercial developments and activities 97

Accelrys 97

Advanced Chemistry Development 97

Aureus Pharma 98

Chemical Computing Group 99

Entelos 99

Gene Network Sciences 101

Leadscope 102

Life Technologies Corporation 102

Molecular Discovery 103

Molecular Networks 104

Noray Bioinformatics 105

Schrödinger 105

Simcyp 105

Simulations Plus 106

TerraBase 107

Tripos 108

Chapter 5 Systems biology models in drug discovery 110

Summary 110

Systems biology: integrative science for drug discovery 111

Predictive biosimulation platforms to aid preclinical research 113

Virtual organs and patients 114

Pathway biology systems: recent commercial developments and activities 116

Ariadne Genomics 116

GeneGo 117

Genomatix 119

Genstruct 120

Ingenuity Systems 122

Merrimack Pharmaceuticals 123

Physiomics 124

Considerations for preclinical models in drug discovery and development 125

Key points and recommendations 125

Appendix 127

Abbreviations and acronyms 127

Primary research methodology 129

References 130

Other sources 130

Index 131

List of Figures

Figure 1.1: Established preclinical ADMET systems and models for drug discovery and development 20

Figure 1.2: Common reasons for a drug candidate's failure 21

Figure 1.3: Key advantages & disadvantages of animal models in preclinical drug development 24

Figure 1.4: Animal models (%) used in preclinical ADMET studies 31

Figure 2.5: Advantages and disadvantages of zebrafish for preclinical ADMET screening in drug discovery and development 53

Figure 2.6: Preclinical ADMET screen types offered by Evotec AG 55

Figure 2.7: Rationale for use of Drosophila as preclinical model for neurobiological disease 66

Figure 4.8: Factors limiting the use of in silico ADMET models 96

Figure 5.9: Drivers of systems biology in pharmaceutical R&D 112

List of Tables

Table 1.1: Routine screens to assess ADME of drug candidates in discovery 26

Table 2.2: Key advantages of Drosophila in preclinical drug discovery and development 64

Table 3.3: Commonly used cultured cells for in-vitro permeability assays 78

To order this report:

Pharmaceutical Industry: Preclinical Models: Innovative solutions to accelerate drug discovery and development

More Market Research Report

Check our Company Profile, SWOT and Revenue Analysis!

Nicolas Bombourg



US: (805)652-2626

Intl: +1 805-652-2626

-- Analysis of current developments in preclinical ADMET research for drug discovery and development -- Evaluation of the drivers behind innovation in preclinical research. -- Identifies the current trends in ADMET research and how technology companies are developing new models to improve and accelerate discovery and development. -- Analysis of current in-vivo, in-vitro, in-silico, and systems biology models that are advancing toxicity prediction in early drug discovery.

SOURCE Reportlinker

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