F. Hoffmann-La Roche Ltd. , pRED, Pharma Research and Early Development, Discovery Chemistry, CH-4070 Basel, Switzerland.
J Med Chem. 2013 Nov 27;56(22):8955-71. doi: 10.1021/jm400856t. Epub 2013 Aug 22.
Polypharmacology describes the activity of compounds at multiple targets. Current research focuses on two aspects of polypharmacology: (1) unintended polypharmacology can lead to adverse effects; (2) polypharmacology across several disease-relevant targets can improve therapeutic efficacy, prevent drug resistance, or reduce therapeutic-target-related adverse effects. This perspective reviews these interconnected aspects of polypharmacology. The first part discusses the relevance of polypharmacology for the safety of drugs, the mitigation of safety risks, and methods to identify polypharmacological compounds early in the drug discovery process. The second part discusses the advantages of polypharmacology in the treatment of multigenic diseases and infections, and opportunities for drug discovery and drug repurposing. This perspective aims to provide a balanced view on polypharmacology, which can compromise the safety of drugs, but can also confer superior efficacy.
多药理学描述了化合物在多个靶点上的活性。当前的研究集中在多药理学的两个方面：（1）非预期的多药理学可能导致不良反应；（2）针对多个与疾病相关靶点的多药理学可以提高治疗效果、预防耐药性或减少治疗靶点相关的不良反应。本观点综述了多药理学的这些相互关联的方面。第一部分讨论了多药理学对药物安全性的相关性、减轻安全风险的方法，以及在药物发现过程早期识别多药理学化合物的方法。第二部分讨论了多药理学在多基因疾病和感染治疗中的优势，以及药物发现和药物再利用的机会。本观点旨在提供一个关于多药理学的平衡观点，多药理学可以降低药物的安全性，但也可以赋予更高的疗效。
