Overview of Drug Polypharmacology and Multitargeted Molecular Design

The "one drug, one target, and one disease" model is partially contributing to the increased failures of clinical trials due to its lacking consideration of side effects or toxicities in the early stage of drug discovery and development. To tackle this issue, an alternative approach is being adopted to study simultaneous interactions of small molecules with multiple specific targets, also known as polypharmacology. It allows exploration of drug multitargeting activities and facilitates potential repositioning. Although exhaustive polypharmacology studies in vitro or in vivo is not practical, computational methods are being developed and have significantly driven the field forward. In this article, we discuss the status of drug polypharmacology and review the current state-of-the-art in silico methods that are used for rational design of multitargeted therapeutics to treat complex diseases such as cancer.