{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T19:36:02Z","timestamp":1794512162660,"version":"4.9.1"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273772"],"award-info":[{"award-number":["82273772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22277006"],"award-info":[{"award-number":["22277006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22307003"],"award-info":[{"award-number":["22307003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7242195"],"award-info":[{"award-number":["7242195"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7212152"],"award-info":[{"award-number":["7212152"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1016\/j.ejmech.2024.116881","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T01:59:27Z","timestamp":1726711167000},"page":"116881","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Scaffold hopping-driven optimization for the identification of NLRP3 inhibitors as potential gout therapeutics"],"prefix":"10.1016","volume":"279","author":[{"given":"Cheng","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Xiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangren","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-4015","authenticated-orcid":false,"given":"Zhenming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ejmech.2024.116881_bib1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41590-019-0548-1","article-title":"Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation","volume":"21","author":"Zewinger","year":"2020","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.ejmech.2024.116881_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106625","article-title":"The NLRP3 inflammasome in depression: potential mechanisms and therapies","volume":"187","author":"Xia","year":"2023","journal-title":"Pharmacol. Res."},{"issue":"12","key":"10.1016\/j.ejmech.2024.116881_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/cells13120995","article-title":"Elevated NLRP3 inflammasome activation is associated with Motor neuron degeneration in ALS","volume":"13","author":"Cihankaya","year":"2024","journal-title":"Cells"},{"issue":"25","key":"10.1016\/j.ejmech.2024.116881_bib4","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2316551121","article-title":"Inhibition of NLRP3 inflammasome activation by A20 through modulation of NEK7","volume":"121","author":"Yu","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ejmech.2024.116881_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2024.122813","article-title":"NLRP3 Inflammasome: a central player in renal pathologies and nephropathy","volume":"351","author":"Henedak","year":"2024","journal-title":"Life Sci."},{"issue":"6","key":"10.1016\/j.ejmech.2024.116881_bib6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/13543776.2023.2239502","article-title":"A patent review of NLRP3 inhibitors to treat autoimmune diseases","volume":"33","author":"Xu","year":"2023","journal-title":"Expert Opin. Ther. Pat."},{"issue":"4","key":"10.1016\/j.ejmech.2024.116881_bib7","doi-asserted-by":"crossref","first-page":"395","DOI":"10.4062\/biomolther.2023.099","article-title":"NLRP3 inflammasome as therapeutic targets in inflammatory diseases","volume":"31","author":"Prakash","year":"2023","journal-title":"Biomol Ther"},{"issue":"4","key":"10.1016\/j.ejmech.2024.116881_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.berh.2021.101719","article-title":"Treatment advances in gout","volume":"35","author":"Stamp","year":"2021","journal-title":"Best Pract Res Cl Rh"},{"issue":"10287","key":"10.1016\/j.ejmech.2024.116881_bib9","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/S0140-6736(21)00569-9","volume":"397","author":"Dalbeth","year":"2021","journal-title":"Gout. Lancet"},{"issue":"7081","key":"10.1016\/j.ejmech.2024.116881_bib10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2024.116881_bib11","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.abb.2019.01.031","article-title":"The NLRP3 inflammasome - interleukin 1 pathway as a therapeutic target in gout","volume":"670","author":"Szekanecz","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"issue":"13","key":"10.1016\/j.ejmech.2024.116881_bib12","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1016\/j.bmc.2017.05.010","article-title":"Potential anti-gout constituents as xanthine oxidase inhibitor from the fruits of Stauntonia brachyanthera","volume":"25","author":"Liu","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116881_bib13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejmech.2017.03.002","article-title":"Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor","volume":"131","author":"Kaur","year":"2017","journal-title":"Eur. J. Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2024.116881_bib14","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/14786419.2011.652960","article-title":"A new lupane triterpene from Tetracera scandens L., xanthine oxidase inhibitor","volume":"27","author":"Nguyen","year":"2013","journal-title":"Nat. Prod. Res."},{"key":"10.1016\/j.ejmech.2024.116881_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107381","article-title":"Discovery of digallic acid as XOD\/URAT1 dual target inhibitor for the treatment of hyperuricemia","volume":"147","author":"Zheng","year":"2024","journal-title":"Bioorg. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2024.116881_bib16","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.2165\/11205470-000000000-00000","article-title":"Oral colchicine (colcrys (R)) in the treatment and prophylaxis of gout","volume":"70","author":"Yang","year":"2010","journal-title":"Drugs"},{"issue":"2","key":"10.1016\/j.ejmech.2024.116881_bib17","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.annemergmed.2018.02.004","article-title":"Are corticosteroids superior to nonsteroidal anti-inflammatory drugs in the treatment of acute gout?","volume":"72","author":"Watkins","year":"2018","journal-title":"Ann. Emerg. Med."},{"issue":"4","key":"10.1016\/j.ejmech.2024.116881_bib18","doi-asserted-by":"crossref","first-page":"JC14","DOI":"10.7326\/ACPJC-2017-166-4-014","article-title":"Guideline: in acute gout, steroids, NSAIDs, or low-dose colchicine recommended; lifestyle changes not supported","volume":"166","author":"Palabindala","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.ejmech.2024.116881_bib19","first-page":"15","article-title":"The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors","volume":"41","author":"Wechalekar","year":"2014","journal-title":"J. Rheumatol."},{"issue":"2","key":"10.1016\/j.ejmech.2024.116881_bib20","first-page":"90","article-title":"The immunological basis in the pathogenesis of gout","volume":"14","author":"Chen","year":"2017","journal-title":"Iran J Immunol"},{"issue":"3","key":"10.1016\/j.ejmech.2024.116881_bib21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat Med"},{"issue":"7904","key":"10.1016\/j.ejmech.2024.116881_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-022-04467-w","article-title":"Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3","volume":"604","author":"Hochheiser","year":"2022","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.ejmech.2024.116881_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/nrd.2018.149","article-title":"Targeting the NLRP3 inflammasome in inflammatory diseases (vol 17, pg 588, 2018)","volume":"17","author":"Mangan","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"issue":"21","key":"10.1016\/j.ejmech.2024.116881_bib24","doi-asserted-by":"crossref","first-page":"14897","DOI":"10.1021\/acs.jmedchem.3c01398","article-title":"Discovery of clinical candidate NT-0796, a brain-penetrant and highly potent NLRP3 inflammasome inhibitor for neuroinflammatory disorders","volume":"66","author":"Harrison","year":"2023","journal-title":"J. Med. Chem."},{"issue":"21","key":"10.1016\/j.ejmech.2024.116881_bib25","doi-asserted-by":"crossref","first-page":"14721","DOI":"10.1021\/acs.jmedchem.2c01250","article-title":"Overcoming preclinical safety obstacles to discover (S)-N-((1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide (GDC-2394): a potent and selective NLRP3 inhibitor","volume":"65","author":"Townsend","year":"2022","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2024.116881_bib26","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1021\/acs.jmedchem.3c02098","article-title":"Discovery of potent, orally bioavailable, tricyclic NLRP3 inhibitors","volume":"67","author":"Velcicky","year":"2024","journal-title":"J. Med. Chem."},{"issue":"19","key":"10.1016\/j.ejmech.2024.116881_bib27","doi-asserted-by":"crossref","first-page":"13428","DOI":"10.1021\/acs.jmedchem.3c00696","article-title":"Discovery of triazinone derivatives as novel, specific, and direct NLRP3 inflammasome inhibitors for the treatment of DSS-induced ulcerative colitis","volume":"66","author":"Li","year":"2023","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116881_bib28","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04947-6","article-title":"Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity","volume":"9","author":"He","year":"2018","journal-title":"Nat. Commun."},{"issue":"7","key":"10.1016\/j.ejmech.2024.116881_bib29","doi-asserted-by":"crossref","first-page":"E1530","DOI":"10.1073\/pnas.1716095115","article-title":"OLT1177, a beta-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation","volume":"115","author":"Marchetti","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"10.1016\/j.ejmech.2024.116881_bib30","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201708689","article-title":"Tranilast directly targets NLRP3 to treat inflammasome-driven diseases","volume":"10","author":"Huang","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ejmech.2024.116881_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115784","article-title":"Discovery of NLRP3 inhibitors using machine learning: identification of a hit compound to treat NLRP3 activation-driven diseases","volume":"260","author":"Shi","year":"2023","journal-title":"Eur. J. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2024.116881_bib32","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1021\/acs.jcim.0c00005","article-title":"TF3P: three-dimensional force fields fingerprint learned by deep capsular network","volume":"60","author":"Wang","year":"2020","journal-title":"J. Chem. Inf. Model."},{"issue":"1","key":"10.1016\/j.ejmech.2024.116881_bib33","doi-asserted-by":"crossref","DOI":"10.1080\/08916934.2024.2310269","article-title":"The role of NLRP3 inflammasome in type 2 inflammation related diseases","volume":"57","author":"Xu","year":"2024","journal-title":"Autoimmunity"},{"issue":"8","key":"10.1016\/j.ejmech.2024.116881_bib34","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1021\/acs.jmedchem.2c00149","article-title":"Synthesis and pharmacological evaluation of new N-sulfonylureas as NLRP3 inflammasome inhibitors: identification of a hit compound to treat gout","volume":"65","author":"Narros-Fernandez","year":"2022","journal-title":"J. Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2024.116881_bib35","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.tibs.2022.10.002","article-title":"The NLRP3 inflammasome: activation and regulation","volume":"48","author":"Xu","year":"2023","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.ejmech.2024.116881_bib36","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11926-023-01128-3","article-title":"Pipeline therapies for gout","volume":"26","author":"Yip","year":"2023","journal-title":"Curr. Rheumatol. Rep."},{"key":"10.1016\/j.ejmech.2024.116881_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114890","article-title":"Recent advances in gout drugs","volume":"245","author":"Shi","year":"2023","journal-title":"Eur. J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424007621?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424007621?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:06:28Z","timestamp":1777529188000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523424007621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":37,"alternative-id":["S0223523424007621"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.116881","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Scaffold hopping-driven optimization for the identification of NLRP3 inhibitors as potential gout therapeutics","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.116881","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"116881"}}