Terstappen Georg C, Schlüpen Christina, Raggiaschi Roberto, Gaviraghi Giovanni
Siena Biotech S.p.A., Via Fiorentina 1, 53100 Siena, Italy.
Nat Rev Drug Discov. 2007 Nov;6(11):891-903. doi: 10.1038/nrd2410.
Recognition of some of the limitations of target-based drug discovery has recently led to the renaissance of a more holistic approach in which complex biological systems are investigated for phenotypic changes upon exposure to small molecules. The subsequent identification of the molecular targets that underlie an observed phenotypic response--termed target deconvolution--is an important aspect of current drug discovery, as knowledge of the molecular targets will greatly aid drug development. Here, the broad panel of experimental strategies that can be applied to target deconvolution is critically reviewed.
认识到基于靶点的药物发现存在一些局限性,最近促使一种更全面的方法得以复兴,即研究复杂生物系统在接触小分子后的表型变化。随后确定观察到的表型反应背后的分子靶点——即靶点反卷积——是当前药物发现的一个重要方面,因为分子靶点的知识将极大地有助于药物开发。在此,对可应用于靶点反卷积的广泛实验策略进行了批判性综述。