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Inhibiting the inflammasome: a chemical perspective

Baldwin, Alex, Brough, David and Freeman, Sally 2015. Inhibiting the inflammasome: a chemical perspective. Journal of Medicinal Chemistry 59 (5) , pp. 1691-1710. 10.1021/acs.jmedchem.5b01091

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Abstract

Inflammasomes are high molecular weight complexes that sense and react to injury and infection. Their activation induces caspase-1 activation and release of interleukin-1β, a pro-inflammatory cytokine involved in both acute and chronic inflammatory responses. There is increasing evidence that inflammasomes, particularly the NLRP3 inflammasome, act as guardians against noninfectious material. Inappropriate activation of the NLRP3 inflammasome contributes to the progression of many noncommunicable diseases such as gout, type II diabetes, and Alzheimer’s disease. Inhibiting the inflammasome may significantly reduce damaging inflammation and is therefore regarded as a therapeutic target. Currently approved inhibitors of interleukin-1β are rilonacept, canakinumab, and anakinra. However, these proteins do not possess ideal pharmacokinetic properties and are unlikely to easily cross the blood–brain barrier. Because inflammation can contribute to neurological disorders, this review focuses on the development of small-molecule inhibitors of the NLRP3 inflammasome.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: American Chemical Society
ISSN: 0022-2623
Last Modified: 20 Mar 2018 12:25
URI: http://orca.cf.ac.uk/id/eprint/110002

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