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| Home > Publications Database > Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation. > print |
| 001 | 138812 | ||
| 005 | 20240321220513.0 | ||
| 024 | 7 | _ | |a 10.4049/jimmunol.1600035 |2 doi |
| 024 | 7 | _ | |a pmid:27521339 |2 pmid |
| 024 | 7 | _ | |a 0022-1767 |2 ISSN |
| 024 | 7 | _ | |a 1047-7381 |2 ISSN |
| 024 | 7 | _ | |a 1048-3233 |2 ISSN |
| 024 | 7 | _ | |a 1550-6606 |2 ISSN |
| 024 | 7 | _ | |a altmetric:28698417 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-05134 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Primiano, Michael J |b 0 |
| 245 | _ | _ | |a Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation. |
| 260 | _ | _ | |a Bethesda, Md. |c 2016 |b Soc. |
| 264 | _ | 1 | |3 online |2 Crossref |b The American Association of Immunologists |c 2016-08-12 |
| 264 | _ | 1 | |3 print |2 Crossref |b The American Association of Immunologists |c 2016-09-15 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1585919153_20528 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a A critical component of innate immune response to infection and tissue damage is the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome, and this pathway and its activation products have been implicated in the pathophysiology of a variety of diseases. NLRP3 inflammasome activation leads to the cleavage of pro-IL-1β and pro-IL-18, as well as the subsequent release of biologically active IL-1β, IL-18, and other soluble mediators of inflammation. In this study, we further define the pharmacology of the previously reported NLRP3 inflammasome-selective, IL-1β processing inhibitor CP-456,773 (also known as MCC950), and we demonstrate its efficacy in two in vivo models of inflammation. Specifically, we show that in human and mouse innate immune cells CP-456,773 is an inhibitor of the cellular release of IL-1β, IL-1α, and IL-18, that CP-456,773 prevents inflammasome activation induced by disease-relevant soluble and crystalline NLRP3 stimuli, and that CP-456,773 inhibits R848- and imiquimod-induced IL-1β release. In mice, CP-456,773 demonstrates potent inhibition of the release of proinflammatory cytokines following acute i.p. challenge with LPS plus ATP in a manner that is proportional to the free/unbound concentrations of the drug, thereby establishing an in vivo pharmacokinetic/pharmacodynamic model for CP-456,773. Furthermore, CP-456,773 reduces ear swelling in an imiquimod cream-induced mouse model of skin inflammation, and it reduces airway inflammation in mice following acute challenge with house dust mite extract. These data implicate the NLRP3 inflammasome in the pathogenesis of dermal and airway inflammation, and they highlight the utility of CP-456,773 for interrogating the contribution of the NLRP3 inflammasome and its outputs in preclinical models of inflammation and disease. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Cytokines |2 NLM Chemicals |
| 650 | _ | 7 | |a Heterocyclic Compounds, 4 or More Rings |2 NLM Chemicals |
| 650 | _ | 7 | |a Inflammasomes |2 NLM Chemicals |
| 650 | _ | 7 | |a Interleukin-18 |2 NLM Chemicals |
| 650 | _ | 7 | |a Interleukin-1alpha |2 NLM Chemicals |
| 650 | _ | 7 | |a Interleukin-1beta |2 NLM Chemicals |
| 650 | _ | 7 | |a MCC-950 |2 NLM Chemicals |
| 650 | _ | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM Chemicals |
| 650 | _ | 7 | |a Sulfones |2 NLM Chemicals |
| 650 | _ | 2 | |a Furans |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Cytokines: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Cytokines: immunology |2 MeSH |
| 650 | _ | 2 | |a Dermatitis: drug therapy |2 MeSH |
| 650 | _ | 2 | |a Dermatitis: immunology |2 MeSH |
| 650 | _ | 2 | |a Dermatitis: physiopathology |2 MeSH |
| 650 | _ | 2 | |a Disease Models, Animal |2 MeSH |
| 650 | _ | 2 | |a Heterocyclic Compounds, 4 or More Rings: administration & dosage |2 MeSH |
| 650 | _ | 2 | |a Heterocyclic Compounds, 4 or More Rings: pharmacology |2 MeSH |
| 650 | _ | 2 | |a Heterocyclic Compounds, 4 or More Rings: therapeutic use |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Immunity, Innate: drug effects |2 MeSH |
| 650 | _ | 2 | |a Inflammasomes: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Inflammation: drug therapy |2 MeSH |
| 650 | _ | 2 | |a Inflammation: immunology |2 MeSH |
| 650 | _ | 2 | |a Inflammation: physiopathology |2 MeSH |
| 650 | _ | 2 | |a Interleukin-18: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Interleukin-18: metabolism |2 MeSH |
| 650 | _ | 2 | |a Interleukin-1alpha: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Interleukin-1alpha: metabolism |2 MeSH |
| 650 | _ | 2 | |a Interleukin-1beta: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Interleukin-1beta: immunology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a NLR Family, Pyrin Domain-Containing 3 Protein: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Pneumonia: drug therapy |2 MeSH |
| 650 | _ | 2 | |a Pneumonia: immunology |2 MeSH |
| 650 | _ | 2 | |a Pneumonia: physiopathology |2 MeSH |
| 650 | _ | 2 | |a Signal Transduction |2 MeSH |
| 650 | _ | 2 | |a Sulfones: administration & dosage |2 MeSH |
| 650 | _ | 2 | |a Sulfones: pharmacology |2 MeSH |
| 650 | _ | 2 | |a Sulfones: therapeutic use |2 MeSH |
| 650 | _ | 2 | |a Indenes |2 MeSH |
| 650 | _ | 2 | |a Sulfonamides |2 MeSH |
| 700 | 1 | _ | |a Lefker, Bruce A |b 1 |
| 700 | 1 | _ | |a Bowman, Michael R |b 2 |
| 700 | 1 | _ | |a Bree, Andrea G |b 3 |
| 700 | 1 | _ | |a Hubeau, Cedric |b 4 |
| 700 | 1 | _ | |a Bonin, Paul D |b 5 |
| 700 | 1 | _ | |a Mangan, Matthew |0 P:(DE-2719)2810930 |b 6 |u dzne |
| 700 | 1 | _ | |a Dower, Ken |b 7 |
| 700 | 1 | _ | |a Monks, Brian G |b 8 |
| 700 | 1 | _ | |a Cushing, Leah |b 9 |
| 700 | 1 | _ | |a Wang, Stephen |b 10 |
| 700 | 1 | _ | |a Guzova, Julia |b 11 |
| 700 | 1 | _ | |a Jiao, Aiping |b 12 |
| 700 | 1 | _ | |a Lin, Lih-Ling |b 13 |
| 700 | 1 | _ | |a Latz, Eicke |0 P:(DE-2719)2000062 |b 14 |u dzne |
| 700 | 1 | _ | |a Hepworth, David |b 15 |
| 700 | 1 | _ | |a Hall, J Perry |0 P:(DE-HGF)0 |b 16 |e Corresponding author |
| 773 | 1 | 8 | |a 10.4049/jimmunol.1600035 |b : The American Association of Immunologists, 2016-08-12 |n 6 |p 2421-2433 |3 journal-article |2 Crossref |t The Journal of Immunology |v 197 |y 2016 |x 0022-1767 |
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