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J Med Chem. 2013 Nov 27;56(22):8955-71. doi: 10.1021/jm400856t. Epub 2013 Aug 22.

Polypharmacology - foe or friend?

Author information

1
F. Hoffmann-La Roche Ltd. , pRED, Pharma Research and Early Development, Discovery Chemistry, CH-4070 Basel, Switzerland.

Abstract

Polypharmacology describes the activity of compounds at multiple targets. Current research focuses on two aspects of polypharmacology: (1) unintended polypharmacology can lead to adverse effects; (2) polypharmacology across several disease-relevant targets can improve therapeutic efficacy, prevent drug resistance, or reduce therapeutic-target-related adverse effects. This perspective reviews these interconnected aspects of polypharmacology. The first part discusses the relevance of polypharmacology for the safety of drugs, the mitigation of safety risks, and methods to identify polypharmacological compounds early in the drug discovery process. The second part discusses the advantages of polypharmacology in the treatment of multigenic diseases and infections, and opportunities for drug discovery and drug repurposing. This perspective aims to provide a balanced view on polypharmacology, which can compromise the safety of drugs, but can also confer superior efficacy.

PMID:
23919353
DOI:
10.1021/jm400856t
[Indexed for MEDLINE]

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