A new paper has been published, and it will also be featured on the cover of the journal. Congrats!


Title : A potent NLRP3 inhibitor effective against both MCC950-sensitive and -resistant inflammation

Journal : Cell Chemical Biology

Link : https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(25)00259-4

Abstract : 

Uncontrolled inflammation is a driving force behind many common and debilitating diseases, including autoimmune conditions, metabolic disorders, and cancer. The NLRP3 inflammasome plays a central role in sensing cellular stress and danger signals, leading to the release of pro-inflammatory cytokines. It has emerged as a key therapeutic target. However, progress toward clinical translation has been hindered by challenges related to drug selectivity and resistance—particularly mutations that render the well-studied inhibitor MCC950 ineffective. This study identifies ZAP-180013 as a structurally distinct NLRP3 inhibitor that overcomes these limitations. In addition to demonstrating robust activity in human immune cells, including those carrying MCC950-resistant NLRP3 variants, ZAP-180013 also reduces inflammation in both systemic and localized disease models. These findings broaden the landscape of inflammasome-targeted therapies and lay the groundwork for addressing currently untreatable forms of inflammatory disease.