| Title |
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
|
|---|---|
| Published in |
Nature Medicine, February 2015
|
| DOI | 10.1038/nm.3806 |
| Pubmed ID | |
| Authors |
Rebecca C Coll, Avril A B Robertson, Jae Jin Chae, Sarah C Higgins, Raúl Muñoz-Planillo, Marco C Inserra, Irina Vetter, Lara S Dungan, Brian G Monks, Andrea Stutz, Daniel E Croker, Mark S Butler, Moritz Haneklaus, Caroline E Sutton, Gabriel Núñez, Eicke Latz, Daniel L Kastner, Kingston H G Mills, Seth L Masters, Kate Schroder, Matthew A Cooper, Luke A J O'Neill |
| Abstract |
The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease. |
X Demographics
The data shown below were collected from the profiles of 59 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 15 | 25% |
| Australia | 8 | 14% |
| Ireland | 7 | 12% |
| Canada | 3 | 5% |
| United Kingdom | 3 | 5% |
| Spain | 1 | 2% |
| New Zealand | 1 | 2% |
| Italy | 1 | 2% |
| Slovenia | 1 | 2% |
| Other | 2 | 3% |
| Unknown | 17 | 29% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 32 | 54% |
| Scientists | 15 | 25% |
| Practitioners (doctors, other healthcare professionals) | 6 | 10% |
| Science communicators (journalists, bloggers, editors) | 6 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 1,350 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 6 | <1% |
| Germany | 3 | <1% |
| United States | 3 | <1% |
| France | 2 | <1% |
| China | 2 | <1% |
| Ireland | 2 | <1% |
| United Kingdom | 2 | <1% |
| Italy | 1 | <1% |
| Austria | 1 | <1% |
| Other | 4 | <1% |
| Unknown | 1324 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 254 | 19% |
| Researcher | 215 | 16% |
| Student > Bachelor | 152 | 11% |
| Student > Master | 150 | 11% |
| Other | 72 | 5% |
| Other | 226 | 17% |
| Unknown | 281 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 255 | 19% |
| Biochemistry, Genetics and Molecular Biology | 197 | 15% |
| Medicine and Dentistry | 185 | 14% |
| Immunology and Microbiology | 149 | 11% |
| Neuroscience | 75 | 6% |
| Other | 169 | 13% |
| Unknown | 320 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 258. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 February 2024.
All research outputs
#144,265
of 25,837,817 outputs
Outputs from Nature Medicine
#643
of 9,407 outputs
Outputs of similar age
#1,516
of 273,199 outputs
Outputs of similar age from Nature Medicine
#5
of 67 outputs
Altmetric has tracked 25,837,817 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,407 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 105.6. This one has done particularly well, scoring higher than 93% of its peers.
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We're also able to compare this research output to 67 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.