Knowledge-Based Drug Repurposing: A Rational Approach Towards the Identification of Novel Medical Applications of Known Drugs

Drug repurposing/reprofiling has attracted considerable attention during the last decade. The object of such approach is to discover second or further medical uses of known chemicals, i. e. targeting existing, withdrawn or abandoned drugs, or yet to be pursued clinical candidates to new disease areas. Recently (2011-2012), the US and UK governments launched public-private joint initiatives towards finding new uses of previously shelved compounds (drug rescue). While in the past repurposing emerged from serendipitous findings and/or from rational exploitation of drug side-effects (e.g. sildenafil, aspirin), the current tendency in the drug development field focuses on knowledge-based drug repurposing, particularly, computer-aided repositioning approaches. The present chapter reviews different cheminformatic and bioinformatic applications, as well as high-throughput literature analysis, oriented to the discovery of new medical uses of known drugs. Applications of such strategies to the discovery of innovative medications for neglected or rare diseases are discussed. Finally, we also review publicly available resources (e.g. chemical libraries) valuable for reprofiling.

Keywords: Bioinformatics, cheminformatics, drug reprofiling, drug repurposing, indication expansion, indication switching, literature-based drug repositioning, neglected diseases, network-based drug repositioning.