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Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases.

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.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Li P,Chen J,Wang J,Zhou W,Wang X,Li B,Tao W,Wang W,Wang Y,Yang L

doi

10.1016/j.jep.2013.07.001

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

93-107

issue

1

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(13)00490-X

journal_volume

151

pub_type

杂志文章

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