Knowledge-Based Drug Repurposing: A Rational Approach Towards the Identification of Novel Medical Applications of Known Drugs
Pp. 44-81 (38)
Carolina L. Bellera, Mauricio E. Di Ianni, María L. Sbaraglini, Eduardo A. Castro, Luis E. Bruno-Blanch and Alan Talevi
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known chemicals, i. e. targeting existing, withdrawn or abandoned drugs, or yet to be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.
Bioinformatics, cheminformatics, drug reprofiling, drug repurposing,
indication expansion, indication switching, literature-based drug repositioning,
neglected diseases, network-based drug repositioning.
Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, Buenos Aires, Argentina.