Peng Li1, Jianxin Chen2, Jinan Wang1, Wei Zhou1, Xia Wang1, Bohui Li1, Weiyang Tao1, Wei Wang3, Yonghua Wang1, Ling Yang4. 1. Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China. 2. Beijing University of Chinese Medicine, Beijing 100029, China. 3. Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: wangwei@bucm.edu.cn. 4. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
Abstract
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.
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.