Promiscuity profiles of bioactive compounds: potency range and difference distributions and the relation to target numbers and families

Abstract

Compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. Promiscuity is the origin of polypharmacology, which is an intensely investigated topic in pharmaceutical research. In compound promiscuity analysis, potency range and difference criteria have thus far not been considered. Herein, we derive through systematic data mining and computational analysis comprehensive profiles of promiscuous compounds from medicinal chemistry sources by combining potency and target information and identify a prevalent promiscuity phenotype across current pharmaceutical targets. Potency measurement type-dependent differences are taken into account. On the basis of our analysis, the majority of promiscuous compounds are active in the sub-μM range against 2 to 5 targets from the same family and display only relatively small potency differences against these targets. Other promiscuity profiles are less frequently observed.