Department of Computer Science, Hunter College, The City University of New York, New York, New York 10065, USA.
Annu Rev Pharmacol Toxicol. 2012;52:361-79. doi: 10.1146/annurev-pharmtox-010611-134630. Epub 2011 Oct 17.
Polypharmacology, which focuses on designing therapeutics to target multiple receptors, has emerged as a new paradigm in drug discovery. Polypharmacological effects are an attribute of most, if not all, drug molecules. The efficacy and toxicity of drugs, whether designed as single- or multitarget therapeutics, result from complex interactions between pharmacodynamic, pharmacokinetic, genetic, epigenetic, and environmental factors. Ultimately, to predict a drug response phenotype, it is necessary to understand the change in information flow through cellular networks resulting from dynamic drug-target interactions and the impact that this has on the complete biological system. Although such is a future objective, we review recent progress and challenges in computational techniques that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes.
多药理学专注于设计针对多种受体的治疗药物，已成为药物发现的新范例。多药理学效应是大多数（如果不是全部）药物分子的属性。药物的疗效和毒性，无论是设计为单靶点还是多靶点治疗药物，都是药效学、药代动力学、遗传、表观遗传和环境因素之间复杂相互作用的结果。最终，要预测药物反应表型，就必须了解动态药物-靶相互作用导致的细胞网络信息流的变化，以及这对完整生物系统的影响。尽管这是一个未来的目标，但我们回顾了最近在计算技术方面的进展和挑战，这些技术可以预测和分析体外和体内的药物反应表型。
