天然产物：1981 年至 2010 年 30 年间的新药来源。
Natural products as sources of new drugs over the 30 years from 1981 to 2010.
机构信息
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.
出版信息
J Nat Prod. 2012 Mar 23;75(3):311-35. doi: 10.1021/np200906s. Epub 2012 Feb 8.
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.
这篇综述是对本杂志 1997 年、2003 年和 2007 年发表的三篇综述的更新和扩充。对于所有批准的治疗药物，时间范围已延长至涵盖 1981 年 1 月 1 日至 2010 年 12 月 31 日，针对全球所有疾病，以及 1950 年（迄今为止最早确定的时间）至 2010 年 12 月，针对全球所有批准的抗肿瘤药物。我们继续使用我们的二级细分，即“天然产物模拟物”或“NM”，加入原始的主要分类，并添加了一个新的命名，“天然产物植物药”或“NB”，以涵盖那些已被 FDA 和类似组织确认为药物实体的植物“定义混合物”。从呈现的数据来看，天然产物作为新型结构的来源，而不一定是最终的药物实体，仍然具有生命力。因此，在癌症领域，在大约从 20 世纪 40 年代至今的时间框架内，175 种小分子药物中，有 131 种，即 74.8%，不是“S”（合成），其中 85 种，即 48.6%，实际上是天然产物或直接从中衍生而来。在其他领域，天然产物结构的影响非常显著，正如预期的那样，抗感染领域依赖于天然产物及其结构。尽管组合化学技术已成功作为优化结构的方法，并在许多最近批准的药物的优化中得到了非常成功的应用，但在这 30 年的时间框架内，我们只能确定一种作为药物批准的全新组合化合物。我们希望引起读者的注意，即越来越认识到大量的天然产物药物/先导化合物实际上是由微生物产生的，或者是微生物与“从中分离出来的宿主”相互作用产生的，因此我们认为应该显著扩大天然产物研究这一领域。
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