How were new medicines discovered?
How were new medicines discovered?
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DOI：
10.1038/nrd3480
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发表时间：
2011-07-01
影响因子：
120.1
通讯作者：
Anthony, Jason
中科院分区：
文献类型：
--
作者：
Swinney, David C.;Anthony, Jason
用于确定潜在候选药物的临床前策略包括基于靶标的筛选、表型筛选、天然物质的修饰和基于生物学的方法。为了研究某些策略是否比其他策略在新药发现中更成功，我们分析了1999年至2008年美国食品和药物管理局批准的新分子实体和新生物制剂的发现策略和分子作用机制（MMOA）。在获得批准的259种药物中，75种是具有新的mmoa的首创药物，其中50种（67%）是小分子药物，25种（33%）是生物制剂。结果还表明，在一个主要关注基于靶标的方法的时代，表型筛选对发现一流小分子药物的贡献超过了基于靶标的方法，其中28种和17种药物分别来自这两种方法。我们认为，以靶点为中心的药物研发方法，而不考虑最佳MMOA，可能导致当前药物研发的高损耗率和低生产率。
Preclinical strategies that are used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. To investigate whether some strategies have been more successful than others in the discovery of new drugs, we analysed the discovery strategies and the molecular mechanism of action (MMOA) for new molecular entities and new biologics that were approved by the US Food and Drug Administration between 1999 and 2008. Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches-with 28 and 17 of these drugs coming from the two approaches, respectively-in an era in which the major focus was on target-based approaches. We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.