Designing Approaches to Multitarget Drugs

Plexxikon adopted a fragment-based drug discovery strategy for the design of multitarget drugs that represents an evolution of the procedure followed for the discovery of a family of selective phosphodiesterase (PDE) inhibitors. The fragment-based drug design was successfully applied for the discovery of multitarget protein-protein interaction inhibitors. Moreover, protein-protein interactions do not have natural small molecule partners, not allowing the design of compounds on the basis of the structure of a small natural substrate or ligand. The modern phenotypic screening has been successfully applied for the discovery of antinociceptive multitarget compounds and for RET inhibitors; this kind of approach can be used fruitfully also for drug repurposing. A survey of the literature showed that the most common strategy followed for the design of multitarget drugs is that based on the use of pharmacophores or structure-activity relationship (SAR) around a lead.