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Natural Products as Sources of New Drugs over the Period 1981−2002

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Natural Products Branch and Pharmaceutical Resources Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892
Cite this: J. Nat. Prod. 2003, 66, 7, 1022–1037
Publication Date (Web):June 12, 2003
https://doi.org/10.1021/np030096l
Copyright © Not subject to U.S. Copyright. Published 2003 American Chemical Society and American Society of Pharmacognosy
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    Abstract

    This review is an updated and expanded version of a paper that was published in this journal in 1997. The time frame has been extended in both directions to include the 22 years from 1981 to 2002, and a new secondary subdivision related to the natural product source but applied to formally synthetic compounds has been introduced, using the concept 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, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame. In other areas, the influence of natural product structures is quite marked, particularly in the antihypertensive area, where of the 74 formally synthetic drugs, 48 can be traced to natural product structures/mimics. Similarly, with the 10 antimigraine drugs, seven are based on the serotonin molecule or derivatives thereof. Finally, although combinatorial techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of a number of recently approved agents, we have not been able to identify a de novo combinatorial compound approved as a drug in this time frame.

    *

     To whom correspondence should be addressed at NCI-Frederick, P.O. Box B, Frederick, MD, 21702. Tel:  (301) 846-5387. Fax:  (301) 846-6178. E-mail:  [email protected].

    †

     Natural Products Branch, Developmental Therapeutics Program.

    ‡

     Pharmaceutical Resources Branch, Developmental Therapeutics Program.

    §

     Current address:  1346 34th Ave., Vero Beach, FL 32960.

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