
{"id":4000,"date":"2023-10-03T13:01:19","date_gmt":"2023-10-03T13:01:19","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/poster\/chemogenomic-screening-of-the-nlrp1-pathway\/"},"modified":"2026-01-22T17:10:15","modified_gmt":"2026-01-22T17:10:15","slug":"chemogenomic-screening-of-the-nlrp1-pathway","status":"publish","type":"poster","link":"https:\/\/www.sygnaturediscovery.com\/fr\/poster\/chemogenomic-screening-of-the-nlrp1-pathway\/","title":{"rendered":"Chemogenomic screening of the NLRP1 pathway"},"content":{"rendered":"<p><span data-contrast=\"none\">Inflammasomes are intracellular complexes that play a key role in innate immunity and <a href=\"https:\/\/www.sygnaturediscovery.com\/therapeutic-areas\/inflammation-and-immunology\/\">inflammation<\/a>. While NLRP1 was the first identified inflammasome, its activation mechanism and therapeutic potential have only recently come into focus.<\/span><span data-ccp-props=\"{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"none\">We investigated the pharmacology of NLRP1 by conducting a chemogenomic library screen (LOPAC\u00a9) using a cell reporter assay. We established a 384-well cellular screen using an A549-(NLRP1)-ASC-GFP reporter model (InvivoGen). NLRP1-specific induction of ASC-speck formation and pyroptotic cell death was confirmed using Val-boroPro (VbP). The LOPAC screening identified compounds that either fully or partially activate NLRP1-ASC-speck formation and cell death compared to VbP. We also identified inhibitors of VbP-induced NLRP1 activation. To ensure specificity, we conducted toxicity counter-screens using control NLRP1-null A549-ASC-GFP cells.<\/span><span data-ccp-props=\"{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"none\">In summary, we established a cellular screen for NLRP1 and unveiled compounds that can modulate NLRP1 activity. This approach provides valuable insights into the mechanisms and targets governing NLRP1 function.<\/span><span data-ccp-props=\"{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}\">\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Dive into our investigation of the NLRP1 inflammasome&rsquo;s pharmacology through compound screening. We&rsquo;ve established a cellular screen and unveiled compounds capable of modulating NLRP1 activity, shedding light on its mechanisms and potential targets. Exciting insights await discovery!<\/p>\n","protected":false},"featured_media":2667,"template":"","category":[706,681,709,708,752,688],"class_list":["post-4000","poster","type-poster","status-publish","has-post-thumbnail","hentry","category-assay-development","category-bioscience","category-cell-based-assays","category-high-throughput-screening","category-ii","category-therapeutic-areas"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Chemogenomic screening of the NLRP1 pathway - Sygnature<\/title>\n<meta name=\"description\" content=\"Insights into NLRP1 inflammasome pharmacology through a chemogenomic screen. 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