Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases
Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases
复制标题
药物发现和组合的系统药理学策略及其在心血管疾病中的应用
DOI：
10.1016/j.jep.2013.07.001
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发表时间：
2014-01-10
影响因子：
5.4
通讯作者：
Yang, Ling
中科院分区：
文献类型：
--
作者：
Li, Peng;Chen, Jianxin;Yang, Ling
民族药理学相关性：多靶点疗法是药物发现的一种有前景的范例，预计比单一疗法能产生更高水平的疗效，同时减少不良反应和毒性。具有多成分和多靶点的草药可能成为基于网络的多靶点药物发现的宝贵资源。材料和方法：在本研究中，我们报告了一个用于药物发现和组合的集成系统药理学平台，并以草药治疗心血管疾病为例。结果：首先，在系统水平上构建和检查了疾病特异性药物靶点网络，以捕获用于发现多靶点药物的关键疾病相关生物学。其次，考虑到疾病复杂性和多层次连通性的整合，设计了一个包含文献报道的关联、化学物质和草药药理学的综合数据库。第三，通过计算方法结合药代动力学、化学基因组学、药理学和系统生物学数据进行大规模系统分析并进行实验验证，为复杂疾病的系统药物设计策略提供优质的信息输出。结论：这种整合不同类型技术的策略有望为药物发现和组合创造新的机会。 (C) 2013 年，爱思唯尔爱尔兰有限公司出版。
Ethnopharmacological relevance: Multi-target therapeutics is a promising paradigm for drug discovery which is expected to produce greater levels of efficacy with fewer adverse effects and toxicity than monotherapies. Medical herbs featuring multi-components and multi-targets may serve as valuable resources for network-based multi-target drug discovery.Materials and methods: In this study, we report an integrated systems pharmacology platform for drug discovery and combination, with a typical example applied to herbal medicines in the treatment of cardiovascular diseases.Results: First, a disease-specific drug-target network was constructed and examined at systems level to capture the key disease-relevant biology for discovery of multi-targeted agents. Second, considering an integration of disease complexity and multilevel connectivity, a comprehensive database of literature-reported associations, chemicals and pharmacology for herbal medicines was designed. Third, a large-scale systematic analysis combining pharmacokinetics, chemogenomics, pharmacology and systems biology data through computational methods was performed and validated experimentally, which results in a superior output of information for systematic drug design strategies for complex diseases.Conclusions: This strategy integrating different types of technologies is expected to help create new opportunities for drug discovery and combination. (C) 2013 Published by Elsevier Ireland Ltd.