title: Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Jinan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Bohui
authors.initials: B
authors.lastname: Li
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Weiyang
authors.initials: W
authors.lastname: Tao
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: wangwei@bucm.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling 712100, Shaanxi, China; College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000737:chemistry* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery; D006801:Humans; D028321:Plant Preparations / Q000737:chemistry* / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry*; D012984:Software; D049490:Systems Biology / Q000379:methods
chemical_list: D002317:Cardiovascular Agents; D028321:Plant Preparations
keywords: A5L; ADME; Absorption, distribution, metabolism and elimination; Arachidonate 5-lipoxygenase; B1AR; CDK2; CT; CVD; Cardiovascular diseases; Carthamus tinctorius; CgmpA; Cyclin dependent kinase 2; DD network; DSH; DT network; Drug discovery and combination; Drug–drug network; Drug–target network; ERB; Estrogen receptor beta; FC; Fructus Cartaegi; M2; MAPK14; Mitogen-activated protein kinase14; Muscarinic acetylcholine receptor 2; NOSE; Nitric-oxide synthase endothelial; OB; Oral bioavailability; PGS; PPAR; Peroxisome proliferator-activaed receptor gamma; Prostaglandin g/h sythase1; RSM; RSM, FC and CT; Radix Salviae Miltiorrhizae; Systems biology; Systems pharmacology; TS; TT network; TTD; Tanimoto similarity; Target–target network; Therapeutic Target Database; beta-1 adrenergic receptor; cGMP-inhibited 3′,5′-cyclic phosphodiesterase A