Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.

Multifactorial diseases, Combination therapy, multitarget drug discovery, network pharmacology, multitargetdirected ligands, designed multiple ligands

Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro, 6, 40126 Bologna, Italy.