Natural Products as Sources of New Drugs over the Last 25 Years英文文献资料.pdfVIP

J. Nat. Prod. 2007, 70, 461477 461 Natural Products as Sources of New Drugs over the Last 25 Years⊥ David J. Newman* and Gordon M. Cragg Natural Products Branch, De elopmental Therapeutics Program, Diision of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick, P.O. Box B, Frederick, Maryland 21702 Recei ed October 10, 2006 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 251/2 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 noo combinatorial compound approved as