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  • Natural products in the HTS paradigm

    Author(s)
    Camp, David
    Griffith University Author(s)
    Camp, David B.
    Year published
    2006
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    Abstract
    The wealth of chemical diversity that has evolved with biological diversity has been used as a source of medicines by indigenous peoples for thousands of years.1,2 Research into natural products reached a peak in the period from 1970-80. Of the 877 small molecule New Chemical Entities (NCEs) arising between 1981 and 2002, 49% were natural products, or derived from them.3 However, by the 1990s research on natural products by the pharmaceutical industry was declining.4 This decline was due to various factors, including the low throughput of screening/isolation of natural product extracts. Drug discovery turned to high throughput ...
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    The wealth of chemical diversity that has evolved with biological diversity has been used as a source of medicines by indigenous peoples for thousands of years.1,2 Research into natural products reached a peak in the period from 1970-80. Of the 877 small molecule New Chemical Entities (NCEs) arising between 1981 and 2002, 49% were natural products, or derived from them.3 However, by the 1990s research on natural products by the pharmaceutical industry was declining.4 This decline was due to various factors, including the low throughput of screening/isolation of natural product extracts. Drug discovery turned to high throughput screening of large libraries of pure compounds synthesised via combinatorial chemistry.4 However, because the chemical diversity of these libraries was not always relevant to biological function, this approach has not been as successful as was hoped.5 Despite the downturn in natural product research in the 80s and early 90s, the potential of natural products as a source of new drugs remains undeniable, and is strongly reflected in the market data. In 2002, drugs derived in whole or in part from natural products, or based on natural product templates, attracted US$20.5 billion in revenue for their respective manufacturers, a figure up 8.2% since 2000.3,6,7 The potential rewards from natural product drug discovery are massive despite being regarded by some as a risky, speculative "fishing expedition" with no guarantee of finding compounds of interest. Timelines, governed by the separation of compounds from extracts using bioassay-guided fractionation, are slower than alternative lead generation strategies. This presentation outlines various process improvements implemented at Natural Product Discovery (NPD) that have streamlined the conventional biodiscovery paradigm. The efficiency gains facilitate delivery of novel chemical leads from NP screening within timelines expected by big pharma and complement HTS as a lead generation strategy. (1) Brohm, D. Angew. Chem. Int. Ed. Engl. 2002, 41, 307-311. (2) Breinbauer, R.; Vetter, I. R.; Waldmann, H. Angew. Chem., Int. Ed. 2002, 41, 2878-2890. (3) Newman, D. J.; Cragg, G. M.; Snader, K. M. Nat. Prod. Rep. 2000, 17, 215-234. (4) Koehn, F. E.; Carter, G. T. Nature Rev. Drug Discov. 2005, 4, 206-220. (5) Wess, G.; Urmann, M.; Sickenberger, B. Angew. Chem. Int. Ed. Engl. 2001, 40, 3341-3350. (6) Cragg, G. M.; Newman, D. J.; Snader, K. M. J. Nat. Prod. 1997, 60, 52-60. (7) Cragg, G. M.; Newman, D. J.; Weiss, R. B. Seminar Oncol. 1997, 24, 156-163.
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    Conference Title
    Natural products in the HTS paradigm
    Publication URI
    http://hdl.handle.net/10072/13166
    Collection
    • Conference outputs

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