Compound promiscuity: what can we learn from current data?

The specificity paradigm that assigns central relevance to achieving target specificity of drug candidates has recently been revisited. Evidence is mounting that polypharmacological drug behavior is often responsible for therapeutic efficacy suggesting the consideration of new drug development strategies. Target promiscuity of compounds is at the origin of polypharmacology. For many bioactive compounds, multiple target annotations are available indicating that compound promiscuity is a general phenomenon. However, careful analysis of compound activity data reveals that the degree of apparent promiscuity is strongly influenced by data selection criteria and the type of activity measurements that are considered. Furthermore, promiscuity involving unrelated targets is less common. Apparent target promiscuity might often better be interpreted as activity promiscuity in different assays.