The success of mechanism-based drug discovery depends on the definition of the drug target. ![]() ![]() With this mapping, we explored the footprint of target classes across disease areas, investigated the success of privileged target families and compiled a list of drug target orthologues for standard model organisms to develop a foundation for the deeper understanding of species differences, cross-species drug repositioning and applicability of animal models. We also mapped each drug (and thereby target) to the WHO Anatomical Therapeutic Chemical Classification System code as a way of obtaining a standard therapeutic indication for them. We emphasize that even with a well-defined concept of efficacy there are challenges in making a clean unambiguous assignment in many cases, especially regarding how to treat protein complexes or drugs that bind to a number of closely related gene products. These include 667 human-genome-derived proteins targeted by drugs for human disease. We curated a total of 893 human and pathogen-derived biomolecules through which 1,578 FDA-approved drugs act. We assigned to each drug their respective efficacy target or target set from the prescribing information and/or the scientific literature. ![]() In this article, we synthesized and built on our previous approaches and systematically recompiled and comprehensively annotated the current list of drugs approved by the US FDA. It is also increasingly important for efforts to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. The definition of a drug target is crucial to the success of mechanism-based drug discovery.
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