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PMID: 22316239 Published · ppublish English Historical Article Journal Article Review

Natural products as sources of new drugs over the 30 years from 1981 to 2010.

Journal of natural products ·Vol. 75 ·No. 3 ·2012-03-23 ·Pages 311-35

Newman DJ, Cragg GM

Abstract

This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 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 and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations. 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 175 small molecules, 131, or 74.8%, are other than "S" (synthetic), with 85, or 48.6%, 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 anti-infective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully 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 30-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.

MeSH Terms
Biological Products Combinatorial Chemistry Techniques Drug Approval History, 20th Century History, 21st Century Molecular Structure Pharmacology/trends Research
Chemicals
Biological Products
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Newman David J
Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick, P.O. Box B, Frederick, Maryland 21702, United States. newmand@mail.nih.gov
Cragg Gordon M
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Article Info
Journal
Journal of natural products
Abbr.
J Nat Prod
ISSN
1520-6025
DOI
10.1021/np200906s
Email
newmand@mail.nih.gov
Published
2012-03-23
Epub
2012-00-08
Pages
311-35
Language
English
Region
United States
NLM ID
7906882
PMCID
PMC3721181
Subset
IM
Grants
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source DOI: 10.1021/np200906s PMC Full Text View journal details
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