Zhang Wenjuan, Bai Yaofei, Wang Yonghua, Xiao Wei
Department of Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
State Key Laboratory of New-tech for Chinese MedicinePharmaceutical Process, Lianyungang, Jiangsu, 222001, China.
Curr Pharm Des. 2016;22(21):3171-81. doi: 10.2174/1381612822666160224142812.
The complexity of diseases has led to recent interest in polypharmacology, which suggests that many effective drugs specially modulate multiple targets. Drugs with multiple targets can provide a superior therapeutic effect and decrease in side effect profile compared to ligands with single target, especially in the treatment of complex diseases, such as tumors, nervous system diseases and inflammatory diseases. The network-based polypharmacology holds the promise of expanding the opportunity for novel targets and drug identification. However, it faces considerable challenges to how multi-target drugs can be rationally designed from the network pharmacology perspective, particularly for combinations of targets that are structurally divergent.
In this review, we focus on the pharmacological properties of current polypharmacology, discuss potential novel drug indication arising from drug repurposing, and introduce approaches to the rational design of multi-target drugs.
As a result, we highlighted the features of polypharmacology. Also, we have presented some computational methods to predict the potential novel multi-target drugs with lower toxicity and higher efficacy. Moreover, network analysis might play important role in repositioning drugs that modulate targets involved in different pathologies.
This perspective aims to provide a global view on polypharmacology, which is the foundation of the next paradigm in drug discovery.
疾病的复杂性引发了近期对多药理学的关注，这表明许多有效药物可特异性调节多个靶点。与单一靶点配体相比，多靶点药物可提供更优的治疗效果并降低副作用，尤其在治疗肿瘤、神经系统疾病和炎症性疾病等复杂疾病时。基于网络的多药理学有望拓展新靶点和药物识别的机会。然而，从网络药理学角度合理设计多靶点药物面临诸多挑战，特别是对于结构不同的靶点组合。
在本综述中，我们聚焦当前多药理学的药理特性，讨论药物重新定位产生的潜在新药物适应症，并介绍多靶点药物的合理设计方法。
因此，我们突出了多药理学的特征。此外，我们还介绍了一些计算方法，以预测毒性更低、疗效更高的潜在新型多靶点药物。而且，网络分析在重新定位调节参与不同病理过程靶点的药物方面可能发挥重要作用。
本观点旨在提供关于多药理学的全局视角，多药理学是药物发现下一范式的基础。
