title: Inhibiting the Inflammasome: A Chemical Perspective.
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.
authors.affiliation: Manchester Pharmacy School, Faculty of Medical and Human Sciences, The University of Manchester , Stopford Building, Oxford Road, Manchester M13 9PT, U.K.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Baldwin
authors.affiliation: Faculty of Life Sciences, The University of Manchester , AV Hill Building, Oxford Road, Manchester M13 9PT, U.K.
authors.forename: David
authors.initials: D
authors.lastname: Brough
authors.affiliation: Manchester Pharmacy School, Faculty of Medical and Human Sciences, The University of Manchester , Stopford Building, Oxford Road, Manchester M13 9PT, U.K.
authors.forename: Sally
authors.initials: S
authors.lastname: Freeman
mesh_terms: D000818:Animals; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D008968:Molecular Conformation; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058847:Inflammasomes; D054852:Small Molecule Libraries