OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation

Activation of the NLRP3 inflammasome induces maturation of IL-1β and IL-18, both validated targets for treating acute and chronic inflammatory diseases. Here, we demonstrate that OLT1177, an orally active β-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2018-02, Vol.115 (7), p.E1530-E1539
Hauptverfasser:	Marchetti, Carlo, Swartzwelter, Benjamin, Gamboni, Fabia, Neff, Charles P., Richter, Katrin, Azam, Tania, Carta, Sonia, Tengesdal, Isak, Nemkov, Travis, D’Alessandro, Angelo, Henry, Curtis, Jones, Gerald S., Goodrich, Scott A., St. Laurent, Joseph P., Jones, Terry M., Scribner, Curtis L., Barrow, Robert B., Altman, Roy D., Skouras, Damaris B., Gattorno, Marco, Grau, Veronika, Janciauskiene, Sabina, Rubartelli, Anna, Joosten, Leo A. B., Dinarello, Charles A.
Format:	Artikel
Sprache:	eng
Schlagworte:	Activation Adenosine triphosphatase Biological Sciences Blood Caspase Caspase-1 Cryopyrin Efflux Fluorescence resonance energy transfer Gene expression Hematology Immunoprecipitation Inflammasomes Inflammatory diseases Interleukin 18 Leukocytes (neutrophilic) Lipopolysaccharides Macrophages Metabolic rate Metabolism Mice Molecules Monocytes Muscles NF-κB protein Oligomerization Oxidative metabolism Oxidative stress PNAS Plus Potassium Spleen
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