Abstract：
:Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among active compounds. Compared to the original ChEMBL release, a significant increase in the proportion of target promiscuous compounds was observed in the current version. The presence of these compounds led to large-magnitude changes in compound activity-based target and target family relationships and to a reorganization of major target communities. Surprisingly, however, this strong trend toward increasing target promiscuity was largely caused by growth of compounds with exclusive IC(50) measurements. By contrast, compounds with available equilibrium constants, which were also added in large amounts, did not substantially alter compound-based target relationships and notably contribute to increasing target promiscuity. These findings suggest that apparent compound promiscuity is much dependent on experimental conditions under which activities are determined and that care should be taken when evaluating promiscuity and polypharmacology on the basis of assay-dependent activity measurements.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Hu Y,Bajorath Jdoi
10.1021/ci3003304subject
Has Abstractpub_date
2012-10-22 00:00:00pages
2550-8issue
10eissn
1549-9596issn
1549-960Xjournal_volume
52pub_type
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