Navigating from phenotypic screen to clinical candidate: selective targeting the NLRP3 inflammasome

ABSTRACT: The NLRP3 inflammasome plays a pivotal role in host defence and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 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-activity 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

SUBMITTER: Dr. Rosalie Matico 

PROVIDER: S-SCDT-10_1038-S44321-024-00181-4 | biostudies-other |

REPOSITORIES: biostudies-other