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Nat Rev Drug Discov. 2015 Oct;14(10):693-720. doi: 10.1038/nrd4592. Epub 2015 Sep 4.

Dissecting fibrosis: therapeutic insights from the small-molecule toolbox.

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Fibrosis Discovery Performance Unit, Medicines Research Centre, GlaxoSmithKline, Stevenage, SG1 2NY, UK.
Department of Chemistry, Queen Mary University of London, E1 4NS, UK.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.


Fibrosis, which leads to progressive loss of tissue function and eventual organ failure, has been estimated to contribute to ~45% of deaths in the developed world, and so new therapeutics to modulate fibrosis are urgently needed. Major advances in our understanding of the mechanisms underlying pathological fibrosis are supporting the search for such therapeutics, and the recent approval of two anti-fibrotic drugs for idiopathic pulmonary fibrosis has demonstrated the tractability of this area for drug discovery. This Review examines the pharmacology and structural information for small molecules being evaluated for lung, liver, kidney and skin fibrosis. In particular, we discuss the insights gained from the use of these pharmacological tools, and how these entities can inform, and probe, emerging insights into disease mechanisms, including the potential for future drug combinations.

[Indexed for MEDLINE]

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