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Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with\n                    <jats:italic>NLRP3<\/jats:italic>\n                    mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3. In this study, we present the identification of a novel chemical class exhibiting selective and potent inhibition of the NLRP3 inflammasome. Through a comprehensive structure\u2013activity relationship (SAR) campaign, we optimized the lead molecule, compound A, for in vivo applications. Extensive in vitro and in vivo characterization of compound A confirmed the high selectivity and potency positioning compound A as a promising clinical candidate for diseases associated with aberrant NLRP3 activity. This research contributes to the ongoing efforts in developing targeted therapies for conditions involving NLRP3-mediated inflammation, opening avenues for further preclinical and clinical investigations.\n                  <\/jats:p>","DOI":"10.1038\/s44321-024-00181-4","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T05:26:16Z","timestamp":1733721976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 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