title: The role of fragment-based and computational methods in polypharmacology.
abstract: Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery process. Here, we report on fragment-based and computational methods that might accelerate and optimize the discovery of multitarget drugs. In particular, we illustrate that fragment-based approaches can be particularly suited for polypharmacology, owing to the inherent promiscuous nature of fragments. In parallel, we explain how computer-assisted protocols can provide invaluable insights into how to unveil compounds theoretically able to bind to more than one protein. Furthermore, several pragmatic aspects related to the use of these approaches are covered, thus offering the reader practical insights on multitarget-oriented drug discovery projects.
authors.affiliation: Department of Drug Discovery and Development (D3), Istituto Italiano di Tecnologia, I-16163 Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bottegoni
authors.forename: Angelo D
authors.initials: AD
authors.lastname: Favia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans