Natural Product Pharmaceuticals: A diverse approach to drug discovery
Therapeutic / Strategic Management
New discovery technology is making Natural Products (NPs) a more commercially exploitable source of chemical diversity for novel lead compounds.
With innovative isolation and structural characterisation methods for bioactive natural products enabling a massive reduction in the time and cost involved in going from an active extract to a defined molecule is it time for your company to go back to nature?
Scrip's Natural Product Pharmaceuticals: A diverse approach to drug discovery is your comprehensive guide to this area of exciting opportunity, exploring drug discovery emerging from R&D and summarising technical developments and the political debate over access to biodiversity.
It is estimated that 40-50% of all drugs are naturally derived, yet the structural diversity that NPs bring into the drug discovery arena has remained an under-utilised resource within the pharmaceutical industry.
This report answers the questions you are asking:
About the Author
Professor Alan Harvey was the founding Director of the Strathclyde Institute
for Drug Research (SIDR), an interdisciplinary research organisation created
in 1988 at the University of Strathclyde to promote commercially relevant
drug research.
Dr Harvey is the Managing Director of Drug Discovery Ltd, formed in 1998 to undertake commercial development of NP-based activities at SIDR. With an expanding NP library and in-house discovery programmes, the company also contracts its expertise to other pharmaceutical companies.
To visit the Drug Discovery website, please click on the link below:
http://www.drugdiscovery.co.uk
Published: June 2001
Pages: 124
Ref: BS1089E
Price: £695/$1,460/¥167,000
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CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
ABBREVIATIONS
CHAPTER 1 INTRODUCTION
1.1 Background
1.2 Report structure
1.2.1 Chapter 2: Drug discovery strategies: identification and optimisation
1.2.2 Chapter 3: Technical aspects of using natural products in drug discovery and development
1.2.3 Chapter 4: Bioprospecting and biodiversity
1.2.4 Chapter 5: Emerging natural product-derived drugs in clinical development
1.2.5 Chapter 6: Natural product-derived drugs in preclinical development
1.2.6 Chapter 7: Company profiles
CHAPTER 2 DRUG DISCOVERY STRATEGIES: IDENTIFICATION AND OPTIMISATION
2.1 Introduction: the why and how of drug discovery from natural products
2.1.1 Fermentation
2.1.2 Traditional medicines
2.1.3 Technology
2.1.4 Pre-purification
2.1.5 Classical approach to screening
2.1.6 Biodiversity
2.2 Biologically active natural products as lead compounds
2.3 Leads from traditional medicines
2.4 Complementary approaches in a combinatorial chemistry world
2.5 Screening and natural product libraries
2.5.1 Low and high throughput screening
2.5.2 Sources of chemicals for high throughput screening
2.5.3 Availability of natural products for screening
2.5.3.1 Sources of natural product extracts
2.6 Synthesis of natural product-based libraries
2.7 High throughput screening-compatible formats
2.8 Combinatorial genetics: novel 'natural' compound libraries
CHAPTER 3 TECHNICAL ASPECTS OF USING NATURAL PRODUCTS IN DRUG DISCOVERY AND DEVELOPMENT
3.1 Selecting, identifying and collecting samples
3.2 Extracting, processing and storing samples
3.2.1 Extractions
3.2.2 Clean-up and storage
3.2.3 Large-scale processing
3.3 Isolation and purification of active compounds
3.4 Dereplication and structural elucidation
3.5 Screening for activity
3.6 Lead optimisation
3.7 Development issues
3.8 Reliability of supply
3.9 Patenting of natural products
CHAPTER 4 BIOPROSPECTING AND BIODIVERSITY
4.1 Biodiversity: the United Nations Convention on Biological Diversity
4.2 Indigenous resource rights, sustainability and ethical considerations
4.2.1 Rights to bioresources
4.2.2 Value of bioresources
4.3 Sourcing and supply of natural products
4.4 Biological sources: habitats
4.5 Biological sources: novel organisms
4.5.1 Plants
4.5.2 Microbes
4.5.3 Marine
4.5.4 Animals
CHAPTER 5 EMERGING NATURAL PRODUCT-BASED DRUGS IN CLINICAL DEVELOPMENT
5.1 Major contributions from natural products to modern medicine
5.2 Recently launched medicines derived from natural products
5.2.1 Anticancer agents
5.2.1.1 Paclitaxel and docetaxel
5.2.1.2 Podophyllotoxin derivatives
5.2.1.3 Camptothecin derivatives
5.2.1.4 Vinca alkaloids
5.2.2 Immunosuppressants
5.2.3 Neuropharmacological drugs
5.2.4 Anti-infective drugs
5.3 Drugs derived from natural products that are currently in clinical trials
5.3.1 Anticancer compounds
5.3.1.1 Anticancer compounds in Phase I
5.3.1.2 Anticancer compounds in Phase II
5.3.2 Compounds for metabolic diseases
5.3.3 Neuropharmacological compounds
5.3.4 Anti-infectives compounds
5.3.4.1 Antibacterial compounds
5.3.4.2 Antifungal compounds
5.3.4.3 Antiviral compounds
5.4 Commercialisation agreements
CHAPTER 6 NATURAL PRODUCT-BASED DRUGS IN PRECLINICAL DEVELOPMENT
6.1 Projects in the R&D pipeline
6.1.1 Anticancer projects
6.1.1.1 Compounds of marine origin
6.1.1.2 Compounds of plant origin
6.1.1.3 Compounds of microbial origin
6.1.1.4 Semi-synthetic compounds
6.1.2 Anti-infective projects
6.1.2.1 Antibacterial
6.1.3 Antifungal
6.1.3.1 Antiviral
6.1.4 Neuropharmacological projects
6.1.5 Projects aimed at metabolic diseases
6.1.6 Projects directed at other therapeutic areas
6.2 Discovery agreements
6.2.1 Supply of natural products for screening
6.2.2 Supply of technology
6.2.3 Screening collaborations
CHAPTER 7 COMPANY PROFILES
7.1 AnalytiCon Discovery
7.1.1 Principals
7.1.2 The company
7.1.3 Agreements
7.2 bioLeads
7.2.1 Principals
7.2.2 The company
7.2.3 Agreements
7.2.4 R&D portfolio
7.3 BioProspect Ltd
7.3.1 Principals
7.3.2 The company
7.3.3 Agreements
7.4 Calyx Therapeutics
7.4.1 Principals
7.4.2 The company
7.4.3 R&D portfolio
7.5 Cubist Pharmaceuticals
7.5.1 Principals
7.5.2 The company
7.5.3 Agreements
7.5.4 Financial figures
7.5.5 R&D portfolio
7.6 Diversa Corporation
7.6.1 Principals
7.6.2 The company
7.6.3 Agreements
7.7 Drug Discovery Ltd
7.7.1 Principals
7.7.2 The company
7.7.3 Agreements
7.7.4 R&D portfolio
7.8 Entomed
7.8.1 Principals
7.8.2 The company
7.8.3 R&D portfolio
7.9 Indena
7.9.1 Principals
7.9.2 The company
7.9.3 Agreements
7.9.4 R&D portfolio
7.10 Kosan Biosciences
7.10.1 Principals
7.10.2 The company
7.10.3 Agreements
7.10.4 R&D portfolio
7.11 MolecularNature Ltd
7.11.1 Principals
7.11.2 The company
7.12 OSI Pharmaceuticals
7.12.1 Principals
7.12.2 The company
7.12.3 Mergers and acquisitions
7.12.4 Joint ventures
7.12.5 Agreements
7.12.6 Financial figures
7.12.7 R&D portfolio
7.13 Oxford Natural Products
7.13.1 Principals
7.13.2 The company
7.13.3 R&D portfolio
7.14 PharmaMar
7.14.1 Principals
7.14.2 The company
7.14.3 Financial figures
7.14.4 R&D portfolio
7.15 Phytera
7.15.1 Principals
7.15.2 The company
7.15.3 Mergers and acquisitions
7.15.4 Agreements
7.15.5 R&D portfolio
7.16 Phytopharm
7.16.1 Principals
7.16.2 The company
7.16.3 Agreements
7.16.4 Financial figures
7.16.5 R&D portfolio
REFERENCES
USEFUL WEBSITES
FURTHER READING
List of Tables
Table 1.1 Therapeutic categories for natural product-derived drugs recently launched or in clinical development
Table 1.2 Source of natural product-derived drugs recently launched or in clinical development
Table 1.3 Therapeutic categories for natural product-derived drugs in preclinical development
Table 4.1 Articles 15 and 16 from the Convention on Biological Diversity, 5 June 1992
Table 4.2 Sources of commercially available natural product screening collections
Table 4.3 The megadiverse hotspots and their vascular plants
Table 5.1 Recently launched products of natural origin
Table 5.2 Drugs of natural origin in clinical trial or at the registration phase of development
Table 5.3 Therapeutic categories of natural product-derived drugs in clinical trials or at the registration phase of development
Table 5.4 Therapeutic categories of semi-synthetic drugs developed from natural product leads that are in clinical trials or at the registration phase of development
Table 5.5 Drugs of natural product origin in clinical trials for treatment of cancer
Table 5.6 Semi-synthetic drugs derived from natural product leads that are in clinical trials for treatment of cancer
Table 6.1 Sources and therapeutic applications of products of natural origin in preclinical development
Table 6.2 Compounds from natural products with potential activity against HIV
List of Figures
Figure 1.1 Estimated pharmaceutical R&D expenditure (£ billions)
Figure 1.2 Numbers of new chemical entities introduced each year
Figure 2.1 Origin of the 244 drug prototypes used up to 1995
Figure 2.2 Comparison of the coverage of plant families by collections made in the Peruvian Amazon and in the Western Australia.
Figure 2.3 Comparison of the coverage of plant families in the extract library available from Drug Discovery Ltd
Executive summary
Drug discovery (the selection of therapeutic targets, the search for initial bioactive compounds and optimisation of initial 'hits' into development candidates) is under continual scrutiny, as pharmaceutical companies seek to become more efficient and cost-effective.
When declining productivity is coupled with pressures on the pharmaceutical industry to justify the cost effectiveness of new drugs and the uncovering of new potential therapeutic targets from molecular cloning and genomics programmes, there is need for innovation in selecting therapeutic targets and finding lead compounds. Major unmet therapeutic needs make drug discovery necessary, for diseases prevalent in the developed world and in tropical countries.
Early approaches to drug discovery continue to be used � eg making use of traditional natural products, a rich source of therapeutic agents; and the empirical approach of understanding disease pathophysiology and the availability of low molecular weight lead compounds (such as endogenous neurotransmitters). The vast majority of current drug discovery however, relies on molecular approaches, involving defined molecular targets.
Molecular approaches to drug discovery have, in turn, been dominated by high throughput screening (HTS). These screening assays rely on more and more compounds to increase the probability of discovering new drugs. However the key to successful drug discovery is not the number of compounds tested, but the structural diversity of the compounds screened. As Dr William Strohl of Merck Research has stated: 'The pharmaceutical companies that have the best and most diverse chemical collections will ultimately dominate the industry'.
The key question is where can such chemically diverse collections of chemicals come from? There are two main sources of large numbers of compounds: combinatorial chemistry and natural products. Although combinatorial chemistry can provide a large number of compounds for HTS, these tend to lack structural diversity. In contrast, natural products provide a wealth of small molecules with drug-like properties and with incredible structural diversity.
Although natural products have been the main source of medicines in the past, they have been somewhat overlooked in recent times. This is both because of concerns about the perceived complexities of using natural products in HTS and processing (dealt with in Chapter 3), and because of the difficulties of access to biodiversity (see Chapter 4).
These are some of the important issues dealt with in this report, which outlines past successes and current developments in natural product-based drug discovery (see Chapter 2) before exploring the potential benefits of greater use of natural products.
It then goes on to review some of the more significant developments and commercialisation agreements for recently launched natural product-derived drugs (and semi-synthetic derivatives) and the 100 or so drugs in clinical development (see Chapter 5). A review of the 120 projects in preclinical development (see Chapter 6) reveals the most common therapeutic categories for drugs at the preclinical stage and highlights some specific examples under development.
A selection of 16 companies involved in natural product-based drug discovery and development are then profiled (see Chapter 7). These companies range from those providing access to plant extracts, to those providing libraries of purified natural products and early-stage lead compounds, through to those developing important anticancer and other medicinal products from plant medicines and marine samples.
© PJB Publications Ltd. 2001
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