Drug-target and disease networks: polypharmacology in the post-genomic era.
Drug-target and disease networks: polypharmacology in the post-genomic era.
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DOI：
10.1186/2193-9616-1-17
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Bozorgmehr JH
中科院分区：
文献类型：
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作者：
Masoudi-Nejad A;Mousavian Z;Bozorgmehr JH
随着人们对复杂疾病认识的不断加深，药物发现的重点已从公认的“一靶点一药物”模式转向以系统调节多个靶点为目标的“多靶点多药物”模式。鉴定药物与靶蛋白之间的相互作用在基因组药物发现中起着重要的作用，从而发现新的药物或现有药物的新靶点。由于药物-靶点相互作用预测的实验过程费力且昂贵，因此计算机预测是一种有效的方法，可以提供有用的信息来支持实验相互作用数据。在后基因组药物发现中出现的一个重要概念是，基因组学、蛋白质组学、信号学和代谢组学数据的大规模整合可以让我们构建复杂的细胞网络，这将为我们理解生理或病理生理状态的分子基础提供一个新的框架。在后基因组时代，一个新兴的多药理学范式是，药物、靶标和疾病空间可以相互关联，以研究药物对不同空间的影响，它们之间的相互关系可以用于设计药物或鸡尾酒，有效地针对一种或多种疾病状态。因此，未来的目标是创建一个集基因组尺度代谢途径、蛋白-蛋白相互作用网络、基因转录分析为一体的计算平台，为多靶点多药物发现构建一个综合网络。
With the growing understanding of complex diseases, the focus of drug discovery has shifted away from the well-accepted “one target, one drug” model, to a new “multi-target, multi-drug” model, aimed at systemically modulating multiple targets. Identification of the interaction between drugs and target proteins plays an important role in genomic drug discovery, in order to discover new drugs or novel targets for existing drugs. Due to the laborious and costly experimental process of drug-target interaction prediction, in silico prediction could be an efficient way of providing useful information in supporting experimental interaction data. An important notion that has emerged in post-genomic drug discovery is that the large-scale integration of genomic, proteomic, signaling and metabolomic data can allow us to construct complex networks of the cell that would provide us with a new framework for understanding the molecular basis of physiological or pathophysiological states. An emerging paradigm of polypharmacology in the post-genomic era is that drug, target and disease spaces can be correlated to study the effect of drugs on different spaces and their interrelationships can be exploited for designing drugs or cocktails which can effectively target one or more disease states. The future goal, therefore, is to create a computational platform that integrates genome-scale metabolic pathway, protein–protein interaction networks, gene transcriptional analysis in order to build a comprehensive network for multi-target multi-drug discovery.