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      Network pharmacology: the next paradigm in drug discovery

      Nature Chemical Biology
      Springer Science and Business Media LLC

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          Abstract

          The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development--efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets. However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.

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          Author and article information

          Journal
          Nature Chemical Biology
          Nat Chem Biol
          Springer Science and Business Media LLC
          1552-4450
          1552-4469
          November 2008
          October 20 2008
          November 2008
          : 4
          : 11
          : 682-690
          Article
          10.1038/nchembio.118
          18936753
          76a12301-5091-44d3-a405-336d4e243201
          © 2008

          http://www.springer.com/tdm

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