{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:30:08Z","timestamp":1790188208576,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EC\u2010funded RISE, Spanish Ministry of Economy and Competitiveness, Generalitat Valenciana, research council of Tarbiat Modares University","award":["EPIC 690939, SAF2017-84689-R, PROMETEO\/2019\/065, #IG\/39803"],"award-info":[{"award-number":["EPIC 690939, SAF2017-84689-R, PROMETEO\/2019\/065, #IG\/39803"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammasomes are multiprotein complexes that represent critical elements of the inflammatory response. The dysregulation of the best-characterized complex, the NLRP3 inflammasome, has been linked to the pathogenesis of diseases such as multiple sclerosis, type 2 diabetes mellitus, Alzheimer\u2019s disease, and cancer. While there exist molecular inhibitors specific for the various components of inflammasome complexes, no currently reported inhibitors specifically target NLRP3PYD homo-oligomerization. In the present study, we describe the identification of QM380 and QM381 as NLRP3PYD homo-oligomerization inhibitors after screening small molecules from the MyriaScreen library using a split-luciferase complementation assay. Our results demonstrate that these NLRP3PYD inhibitors interfere with ASC speck formation, inhibit pro-inflammatory cytokine IL1-\u03b2 release, and decrease pyroptotic cell death. We employed spectroscopic techniques and computational docking analyses with QM380 and QM381 and the PYD domain to confirm the experimental results and predict possible mechanisms underlying the inhibition of NLRP3PYD homo-interactions.<\/jats:p>","DOI":"10.3390\/ijms23031651","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T08:20:29Z","timestamp":1643617229000},"page":"1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Identification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9067-0678","authenticated-orcid":false,"given":"Soroush","family":"Moasses Ghafary","sequence":"first","affiliation":[{"name":"Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Soriano-Teruel","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, Targeted Therapies on Cancer and Inflammation Laboratory, 46012 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, Polymer Therapeutics Laboratory, 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Lotfollahzadeh","sequence":"additional","affiliation":[{"name":"Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-062X","authenticated-orcid":false,"given":"M\u00f3nica","family":"Sancho","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, Targeted Therapies on Cancer and Inflammation Laboratory, 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Serrano-Candelas","sequence":"additional","affiliation":[{"name":"ProtoQSAR SL, Centro Europeo de Empresas Innovadoras, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Karami","sequence":"additional","affiliation":[{"name":"Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Barigye","sequence":"additional","affiliation":[{"name":"ProtoQSAR SL, Centro Europeo de Empresas Innovadoras, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"},{"name":"MolDrug AI Systems SL, 46018 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Fern\u00e1ndez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, Targeted Therapies on Cancer and Inflammation Laboratory, 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Gozalbes","sequence":"additional","affiliation":[{"name":"ProtoQSAR SL, Centro Europeo de Empresas Innovadoras, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"},{"name":"MolDrug AI Systems SL, 46018 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Nikkhah","sequence":"additional","affiliation":[{"name":"Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Orz\u00e1ez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, Targeted Therapies on Cancer and Inflammation Laboratory, 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Hosseinkhani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-\u03b2","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. 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