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.