Background: It is becoming increasingly accepted that a shift is needed from the traditional target-based approach of drug development towards an integrated perspective of drug action inbiochemical systems. To make this change possible, the interaction networks connecting drugtargets to all components of biological systems must be identified and characterized.Results: We here present an integrative analysis of the interactions between drugs andmetabolism by introducing the concept of metabolic drug scope. The metabolic drug scoperepresents the full set of metabolic compounds and reactions that are potentially affected by a drug.We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Ouranalysis shows that the distribution of metabolic drug scopes is highly uneven, and that drugs canbe classified into several categories based on their scopes. Some of them have small scopescorresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of theunderlying metabolic network. They can furthermore be associated to specific drug therapeuticproperties.Conclusion: These findings demonstrate the relevance of metabolic drug scopes to thecharacterization of drug-metabolism interactions and to understanding the mechanisms of drugaction in a system-wide context.
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