Ulrich Roger, Friend Stephen H
Rosetta Inpharmatics, 12040 115th Avenue NE, Kirkland, Washington 98034, USA.
Nat Rev Drug Discov. 2002 Jan;1(1):84-8. doi: 10.1038/nrd710.
Acting on reports in the late 1980s that most drug candidates fail in development, pharmaceutical discovery programmes responded by devising ways to increase the number of chemicals in the pipeline. With discovery now driven primarily by chemistry and high-throughput screening, the biological effects and, in particular, the toxicity of new compounds are largely not appreciated until a compound enters development. Arguably, this paradigm has produced more failures rather than delivering more successes--with more chemicals to examine, much less is known about any single agent before costly development studies are initiated. The emerging field of toxicogenomics is enabling us to ask detailed questions about drug effects very early on, thereby fundamentally changing our approach to drug discovery.
20世纪80年代末有报告称,大多数候选药物在研发过程中失败,制药研发项目因此采取应对措施,设计各种方法来增加正在研发的化学物质数量。如今,研发主要由化学和高通量筛选驱动,新化合物的生物学效应,尤其是毒性,在化合物进入研发阶段之前很大程度上未得到评估。可以说,这种模式带来了更多失败而非成功——由于要研究的化学物质更多,在启动成本高昂的研发研究之前,对任何一种药物的了解就更少了。毒理基因组学这一新兴领域使我们能够在很早的阶段就对药物效应提出详细问题,从而从根本上改变我们的药物研发方法。