CheMBL data. The freely available ChEMBL database abstracts comprehensive structure-activity data from the medicinal chemical literature and has become an established mainstay for chemoinformatic studies. As discussed above, here we use only those Reference compounds that are reported in scientific journals. A major caveat is that compounds revealed in publications are generally selected to illustrate how various problems were addressed and solved, and therefore carry a risk of being unknowingly biased by author selection. A published medicinal chemistry case history is unlikely to be representative of all that was done, as in practice it discloses only a small proportion of all molecules synthesised in a project. Additionally, in describing structure-activity relationships, there may be a general tendency to emphasise more of the 'better' compounds (more potent, good pharmacokinetics) than the 'poorer' (less potent or metabolically unstable) compounds. While patented compounds are more likely to be representative of what was done, they often lack quantitative potency data, which we required for entry in the Reference compound set. Restricting the analysis to higher potency Reference compounds by introducing a pChEMBL cutoff could in principle improve quality. This was not done for two reasons: 1) it is not possible to compare relative potency values across very widely differing assay formats, and 2) it would reduce the numbers of clinical compounds as well as clinical targets with ≥ 100 Reference compounds.