{"id":13436,"date":"2024-11-25T09:27:00","date_gmt":"2024-11-25T09:27:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&#038;p=13436"},"modified":"2026-01-30T09:59:34","modified_gmt":"2026-01-30T09:59:34","slug":"novel-macrocyclic-nlrp3-inhibitors","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/novel-macrocyclic-nlrp3-inhibitors\/","title":{"rendered":"Novel Macrocyclic NLRP3 Inhibitors"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Stefanie Mesch, <strong>Jonathan Shannon<\/strong>, David Miller, Angus MacLeod, L\u00e9a Bouch\u00e9,<strong> Heather J. Johnston<\/strong>, Kim Matthews, Axel Paehler,<strong> Stuart Best<\/strong>, Wolfgang Guba, <strong>Thomas Alanine<\/strong>, Reena Halai, <strong>Lorna Charge<\/strong>, <strong>Samantha Garside,<\/strong> <strong>Stephen Thom<\/strong>, <strong>Celia Incerti-Pradillos<\/strong>, <strong>Christopher McPherson<\/strong>, <strong>Jokin Carrillo<\/strong>, <strong>Steve St-Gallay<\/strong>, Pierre Rigo, Sonja Schlicht, Alan G. Hendrick, Christian Lerner, Luca Piali, Julie Blaising, Eva Z. Mracsko, Georg Jaeschke, Matthew A. Cooper<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Abstract<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later. Based on MCC950, second-generation inhibitors were developed, aiming to overcome some liabilities such as moderate potency and drug induced liver injury. During the optimization of these (second-generation) inhibitors, conformational studies led to the design of novel macrocycles. Here we report the discovery and optimization of this class of NLRP3 inhibitors.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ref: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39585325\/\">J Med Chem 2024<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[682,713,686,742],"resource_tag":[],"class_list":["post-13436","journal-paper","type-journal-paper","status-publish","hentry","category-chemistry","category-medicinal-chemistry","category-modalities","category-peptides-macrocycles"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Novel Macrocyclic NLRP3 Inhibitors - Sygnature<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/novel-macrocyclic-nlrp3-inhibitors\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Novel Macrocyclic NLRP3 Inhibitors - 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