LMT2368 (1-(4-Chlorophenyl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)urea) Negatively Regulates Inflammation by Inhibiting NLRP3 Inflammasome Activation.

ABSTRACT: Background/Objectives: The dysregulation of NLRP3 inflammasome activation has been established as a key driver of inflammatory disease pathology, which marks NLRP3 as an attractive therapeutic target. However, the clinical development of NLRP3 inhibitors such as MCC950 has been hampered by their associated toxicity profiles, highlighting an unmet clinical need. Methods: Herein, we present LMT2368, a novel urea-based NLRP3 inhibitor identified through screening of urea-based derivatives from our in-house compound library. Results: Biolayer interferometry confirmed direct binding of LMT2368 to the NLRP3 NACHT domain with a (K_D = 27.4 ± 1.2 μM which was superior to MCC950. Molecular docking studies predicted enhanced binding interactions for LMT2368, con

SUBMITTER: Nguyen TU 

PROVIDER: S-EPMC12566734 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature