Monitoring drug promiscuity over time.
Drug promiscuity and polypharmacology are much discussed topics in pharmaceutical research. Experimentally, promiscuity can be studied by profiling of compounds on arrays of targets. Computationally, promiscuity rates can be estimated by mining of compound activity data. In this study, we have assessed drug promiscuity over time by systematically collecting activity records for approved drugs. For 518 diverse drugs, promiscuity rates were determined over different time intervals. Significant differences between the number of reported drug targets and the promiscuity rates derived from activity records were frequently observed. On the basis of high-confidence activity data, an increase in average promiscuity rates from 1.5 to 3.2 targets per drug was detected between 2000 and 2014. These promiscuity rates are lower than often assumed. When the stringency of data selection criteria was reduced in subsequent steps, non-realistic increases in promiscuity rates from ~6 targets per drug in 2000 to more than 28 targets were obtained. Hence, estimates of drug promiscuity significantly differ depending on the stringency with which target annotations and activity data are considered.
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, D-53113, Germany.
Ye
Y
Hu
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, D-53113, Germany.
Jürgen
J
Bajorath