Pognan Francois
AstraZeneca Pharmaceuticals, Safety Assessment, Wilmington, DE 19850, USA.
Pharmacogenomics. 2004 Oct;5(7):879-93. doi: 10.1517/14622416.5.7.879.
Genomics, proteomics and metabonomics are applied to toxicology either as stand-alone technologies or in combination, with the intention of providing a more efficient assessment of the potential side effects of new chemical entities. Two different approaches are taken: a predictive/proactive strategy based on a statistical analogy of 'signatures' of drugs to many known toxicant gene or metabolite fingerprints; and a mechanistic/reactive strategy based on the in-depth biological analysis of the gene, protein or metabolite profiles induced by one or a few compounds of interest. This article focuses on the advantages and disadvantages of these technologies, as well as the many hurdles associated with both these approaches in toxicology that have to be considered before applying them to the assessment of future drugs.
基因组学、蛋白质组学和代谢组学作为独立技术或组合技术应用于毒理学，旨在更有效地评估新化学实体的潜在副作用。采用了两种不同的方法：一种是基于药物“特征”与许多已知毒物基因或代谢物指纹的统计类比的预测性/前瞻性策略；另一种是基于对一种或几种目标化合物诱导的基因、蛋白质或代谢物谱进行深入生物学分析的机制性/反应性策略。本文重点介绍了这些技术的优缺点，以及在将它们应用于未来药物评估之前，毒理学中这两种方法所面临的许多必须考虑的障碍。
