Abstract
Drug repurposing is a creative and resourceful approach to increase the number of therapies by exploiting available and approved drugs. However, identifying new protein targets for previously approved drugs is challenging. Although new strategies have been developed for drug repurposing, there is broad agreement that there is room for further improvements. In this chapter, we review protein-protein interaction (PPI) interface-targeting strategies for drug repurposing applications. We discuss certain features, such as hot spot residue and hot region prediction and their importance in drug repurposing, and illustrate common methods used in PPI networks to identify drug off-targets. We also collect available online resources for hot spot prediction, binding pocket identification, and interface clustering which are effective resources in polypharmacology. Finally, we provide case studies showing the significance of protein interfaces and hot spots in drug repurposing.