Drug promiscuity: problems and promises

ABSTRACT Therapeutic drugs exert their effect by binding to a specific target protein (receptor) and altering its activity. However, all drugs have undesirable side effects, which likely result from the drug binding to other protein targets. Drug promiscuity refers to the ability of small molecule compounds to bind with high affinity to multiple proteins. This drug property is responsible for the problems caused by their side effects. But drug promiscuity also presents a promise: if a drug targets numerous proteins, each interaction may contribute to its therapeutic efficacy. The ability to target multiple genes is especially promising for medicines that treat systemic diseases, including neurological disorders and cancers, which result from gene network problems. Here, I will review both aspects of drug promiscuity and illustrate a potential strategy to move this forward using a computer modeling approach.