Chemical-protein interactome and its application in off-target identification

  • Lun Yang
  • Ke-Jian Wang
  • Li-Shan Wang
  • Anil G. Jegga
  • Sheng-Ying Qin
  • Guang He
  • Jian Chen
  • Yue Xiao
  • Lin He


Drugs exert their therapeutic and adverse effects by interacting with molecular targets. Although designed to interact with specific targets in a desirable manner, drug molecules often bind to unexpected proteins (off-targets). By activating or inhibiting off-targets and the associated biological processes and pathways, the resulting chemical-protein interactions can influence drug reaction directly or indirectly. Exploring the relationship between drug and off-targets and the downstream drug reaction can help understand the polypharmacology of the drug, hence significantly advance the drug repositioning pipeline and the application of personalized medicine in understanding and preventing adverse drug reaction. This review summarizes works on predicting off-targets via chemical-protein interactome (CPI), an interaction strength matrix of drugs across multiple human proteins aiming at exploring the unexpected drug-protein interactions, with a variety of computational strategies, including docking, chemical structure comparison and text-mining etc. Effective recall on previous knowledge, de novo prediction and subsequent experimental validation conferred us strong confidence in these methods. Such studies present prospect of large scale in silico methodologies for off-target discovery with low cost and high efficiency.

Key words

drug repositioning adverse drug reaction chemical-protein interactome off-target off-system 


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Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Lun Yang
    • 1
    • 2
  • Ke-Jian Wang
    • 1
  • Li-Shan Wang
    • 1
  • Anil G. Jegga
    • 3
    • 4
  • Sheng-Ying Qin
    • 1
  • Guang He
    • 1
  • Jian Chen
    • 1
  • Yue Xiao
    • 1
  • Lin He
    • 1
    • 2
    • 5
  1. 1.Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education)Shanghai Jiao Tong UniversityShanghaiChina
  2. 2.Institutes of Biomedical SciencesFudan UniversityShanghaiChina
  3. 3.Division of Biomedical InformaticsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  4. 4.Departments of Pediatrics and Computer ScienceUniversity of CincinnatiCincinnatiUSA
  5. 5.Institute for Nutritional Sciences, Shanghai Institute of Biological SciencesChinese Academy of SciencesShanghaiChina

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