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Natural Products as Sources of New Drugs over the Last 25 Years

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Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick, P.O. Box B, Frederick, Maryland 21702
Cite this: J. Nat. Prod. 2007, 70, 3, 461–477
Publication Date (Web):February 20, 2007
https://doi.org/10.1021/np068054v
Copyright © Not subject to U.S. Copyright. Published 2007 American Chemical Society and American Society of Pharmacognosy

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    Abstract

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    This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 25 1/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than “S” (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the “host from whence it was isolated”, and therefore we consider that this area of natural product research should be expanded significantly.

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     Dedicated to the late Dr. Kenneth L. Rinehart of the University of Illinois at Urbana−Champaign for his pioneering work on bioactive natural products.

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     To whom correspondence should be addressed. Tel:  (301) 846-5387. Fax:  (301) 846-6178. E-mail:  [email protected].

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