Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Curr Top Med Chem. 2018;18(12):949-964. doi: 10.2174/1568026618666180330141351.
Multi-target and combinatorial therapies have been focused for the past several decades. These approaches achieved considerable therapeutic efficacy by modulating the activities of the targets in complex diseases such as HIV-1 infection, cancer and diabetes disease. Most of the diseases cannot be treated efficiently in terms of single gene target, because it involves the cessation of the coordinated function of distinct gene groups. Most of the cellular components work efficiently by interacting with other cellular components and all these interactions together represent interactome. This interconnectivity shows that a defect in a single gene may not be restricted to the gene product itself, but may spread along the network. So, drug development must be based on the network-based perspective of disease mechanisms. Many systematic diseases like neurodegenerative disorders, cancer and cardiovascular cannot be treated efficiently by the single gene target strategy because these diseases involve the complex biological machinery. In clinical trials, many mono-therapies have been found to be less effective. In mono-therapies, the long term treatment, for the systematic diseases make the diseases able to acquired resistance because of the disease nature of the natural evolution of feedback loop and pathway redundancy. Multi-target drugs might be more efficient. Multi-target therapeutics might be less vulnerable because of the inability of the biological system to resist multiple actions. In this study, we will overview the recent advances in the development of methodologies for the identification of drug target interaction and its application in the poly-pharmacology profile of the drug.
多靶点和联合治疗策略是过去几十年来的研究重点。这些方法通过调节 HIV-1 感染、癌症和糖尿病等复杂疾病中靶点的活性,取得了相当大的治疗效果。大多数疾病不能通过单一基因靶点的治疗来有效治疗,因为这涉及到不同基因群协调功能的停止。大多数细胞成分通过与其他细胞成分相互作用而有效地发挥作用,所有这些相互作用共同构成了互作组。这种相互连接性表明,单个基因的缺陷可能不仅限于基因产物本身,而是可能沿着网络传播。因此,药物开发必须基于疾病机制的网络视角。许多系统性疾病,如神经退行性疾病、癌症和心血管疾病,不能通过单一基因靶点策略有效治疗,因为这些疾病涉及复杂的生物学机制。在临床试验中,许多单疗法被发现效果较差。在单疗法中,由于疾病的自然进化反馈回路和途径冗余的性质,系统性疾病的长期治疗会使疾病产生耐药性。多靶点药物可能更有效。多靶点治疗可能不太容易受到影响,因为生物系统无法抵抗多种作用。在这项研究中,我们将综述药物靶点相互作用鉴定方法的最新进展及其在药物多药理学特性中的应用。