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|The Evolving Role Of Natural Products In Drug Discovery|
The Evolving Role Of Natural Products In Drug Discovery
Natural products and their derivatives have historically been invaluable as a source of therapeutic agents. However, in the past decade, research into natural products in the pharmaceutical industry has declined, owing to issues such as the lack of compatibility of traditional natural-product extract libraries with high-throughput screening. However, as discussed in this review, recent technological advances that help to address these issues, coupled with unrealized expectations from current lead-generation strategies, have led to a renewed interest in natural products in drug discovery.
Chemical substances derived from animals, plants and microbes have been a major source of lead compounds for the pharmaceutical industry; of the 877 small-molecule New Chemical Entities (NCEs) introduced between 1981 and 2002, 49% were natural products, semi-synthetic natural product analogues or synthetic compounds based on natural-product pharmacophores.
Despite this success, pharmaceutical research into natural products has experienced a slow decline during the past two decades.
The decreased emphasis in the pharmaceutical industry on the discovery of natural products can be attributed to several factors, including:
the introduction of high-throughput screening against defined molecular targets, which prompted many companies to move from natural-product extract libraries towards 'screen friendly' synthetic chemical libraries.
the development of combinatorial chemistry, which at first offered the prospect of simpler, more drug-like screening libraries of wide chemical diversity
advances in molecular biology, cellular biology and genomics, which increased the number of molecular targets and prompted shorter drug discovery timelines.
However, emerging trends, coupled with unrealized expectations from current R&D strategies, are prompting a renewed interest in natural products as a source of chemical diversity and lead generation. As reviewed here, technological advances, in particular, crucial breakthroughs in separation and structure-determination technologies, are addressing the factors above that led to decreased pharmaceutical research into natural products.
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