Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds

From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical in vitro binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa). The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis.The compounds-per-protein listing generated in this work (provided as a supplementary file) represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability.An important factor in assessing the global progress in drug research is the number of targets for which therapeutic small-molecule modulators have been, are being, or could be, generated. This question was addressed in the landmark publication in 2002 that introduced the "druggable genome" concept [1].This total of approximately 3,000 human proteins was arrived at by homologous family extrapolation from the targets of approved drugs at that time. The count of successful targets was updated in 2006 and stood then at 324, of which the subset of human proteins was 207 [2]. Despite many publications covering this topic, the inclusion of explicit listings of target identifiers, extrinsic to the data sets from which they were derived, are rare, with the partial exception of a poster that included 185 human targets of approved o