As shown for the antithrombotic chemical apixaban in Figure 1A, each chemical drug instance is mapped to its counterpart in IUPHAR (8) and if one is available in ChEBI (9) and for additional pharmacological data. The drug instance is also associated with a disease target using terms from the Disease Ontology (7) and a subcellular location using terms from the GO cellular component ontology (10). When several such drugs form a chemically related family with a single target and mechanism of action, we group them into a set (Figure 1B); that set is then used to create reactions to annotate the shared action (either negative or positive) of the set members on the target. In the case of apixaban and closely related chemical drugs that bind and inhibit Factor Xa both alone and as a complex with Factor Va, a reaction shows drug binding to the complex to form a drug:protein complex that negatively regulates cleavage of Factor II (Figure 1C).
