Shifting from the single to the multitarget paradigm in drug discovery

► Drug discovery is changing from a one target-one drug to a multiple-target model. ► Drug repurposing is a positive application of polypharmacology. ► 'Repurposing' can be extended to chemical libraries other than known drugs. ► Chemogenomics and in vivo testing may uncover 'master key' leads. ► 'Master key' compounds may operate a set of desired 'locks' (multiple-targets).