TABLE 2

Primary and secondary target classifications

Primary and secondary classifications for the unique targets of cancer-relevant HTS assays from PubChem (assay targets), chemical probes (probe targets), and FDA-approved small-molecule cancer drugs (drug targets) shown in Fig. 2. Approved small-molecule drugs were collected from the NCI “A to Z List of Cancer Drugs” (http://www.cancer.gov/about-cancer/treatment/drugs), and the two levels of target classes were defined according to the Panther Classification System (Mi et al., 2013, 2016). Numbers signify the sum of unique targets at or below the indicated target classification level. If a given target was only annotated at the primary level in the database, the sum of primary targets in the table might exceed the sum of secondary targets. Alternatively, the sum of secondary targets can exceed that of primary targets if a given target is linked to multiple secondary Panther protein classifications. An example is thioredoxin reductase 1, cytoplasmic (Uniprot: Q16881), which has a primary classification of oxidoreductase and the secondary classifications reductase and oxidase, due to its potential to catalyze both reactions. Finally, some targets belong to multiple primary classifications, such as nuclear hormone receptors, which fall under both transcription factor and receptor primary classes. The bottom six rows list total numbers for targets that are not currently defined by the Panther Classification System (MicroRNA and bacterial/viral target) or not easily classified (protein–protein interactions, phenotypic target, and pathway target). A total of 20 approved chemotherapeutics is associated with general DNA damage and grouped together under the primary classification of DNA damage.