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Rationalizing Structure and Target Relationships between Current Drugs

  • Research Article
  • Theme: New Paradigms in Pharmaceutical Sciences: In Silico Drug Discovery
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Abstract

A recent analysis of structure and target relationships between current drugs and bioactive compounds has revealed that only a small fraction of drugs that are active against the same or overlapping targets are involved in substructure relationships and/or share the same topology. By contrast, structurally related drugs displayed a tendency to preferentially act against different targets. For bioactive compounds, opposite trends were observed. These surprising findings arising from the global analysis have now been examined in detail by analyzing structure and target relationships between drugs at the level of individual targets and individual drugs and by comparing the results of local (target- or drug-based) and global relationship analysis. On the basis of target-based analysis, on average, only 14% of drugs active against a given target form well-defined structural relationships. In addition, drug-based analysis revealed that on average 72% of all structurally related drugs have no or at most 20% target overlap. Taken together, the results of our current analysis at the level of single targets and drugs rationalize their unexpected structure and target relationships in a consistent manner. These findings also have implications for ligand binding characteristics of popular drug targets and for frequently observed polypharmacological drug behavior.

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Authors and Affiliations

  1. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113, Bonn, Germany

    Ye Hu & Jürgen Bajorath

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  1. Ye Hu
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  2. Jürgen Bajorath
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Correspondence to Jürgen Bajorath.

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Guest Editor: Xiang-Qun Xie

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Hu, Y., Bajorath, J. Rationalizing Structure and Target Relationships between Current Drugs. AAPS J 14, 764–771 (2012). https://doi.org/10.1208/s12248-012-9392-z

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  • DOI: https://doi.org/10.1208/s12248-012-9392-z

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