Medicinal Chemistry Approaches for Multitarget Drugs

It has become increasingly well recognized that modulating multiple biological targets in parallel can be beneficial for treating diseases with complex etiologies such as cancer, asthma, and psychiatric diseases. Both screening and knowledge-based strategies have been used for generating ligands with a specific multitarget profile (designed multiple ligands or DMLs). DML projects are often challenging for medicinal chemists, with the need to appropriately balance affinity for two or more targets while obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. The physicochemical properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued. Since DML projects are resource hungry, an early assessment of the feasibility of any given DML project is essential. Keywords: DML; multitarget; network; synergy