Department of Molecular Genetics, Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada M5S 3E1.
Trends Pharmacol Sci. 2010 Feb;31(2):82-8. doi: 10.1016/j.tips.2009.11.002. Epub 2009 Dec 7.
Although it is commonly recognized that most drugs cause inhibition or activation of function by physically binding to one or more gene products, the direct interactions of bioactive small molecules with specific gene products, or targets, is often not well characterized. From a therapeutic perspective, it is nevertheless essential to know a drug's binding partner(s) to understand the mechanism of action and anticipate possible side effects to avoid costly clinical failures. This knowledge is increasingly important as the prevalence of polypharmacy expands to include drugs that engage multiple targets. This review provides a succinct overview of several recent approaches that employ genetics, proteomics, expression profiling or bioinformatics procedures for the systematic characterization of the targets of bioactive compounds. The continuous improvement and advancement of existing technologies is critically discussed and we offer a perspective on the future of innovative emerging new generation technologies.
虽然人们普遍认为大多数药物通过物理结合到一个或多个基因产物上来抑制或激活功能，但生物活性小分子与特定基因产物（即靶标）的直接相互作用通常还没有很好地表征。从治疗的角度来看，了解药物的结合伙伴对于理解作用机制和预测可能的副作用以避免昂贵的临床失败是至关重要的。随着多药治疗的普及，包括作用于多个靶点的药物，这种知识变得越来越重要。本文综述了几种最近采用遗传学、蛋白质组学、表达谱或生物信息学方法来系统表征生物活性化合物靶标的方法，提供了一个简洁的概述。本文还批判性地讨论了现有技术的不断改进和进步，并对创新的新一代技术的未来提出了看法。
