Tetramethoxystilbene Inhibits NLRP3 Inflammasome Assembly via Blocking the Oligomerization of Apoptosis-Associated Speck-like Protein Containing Caspase Recruitment Domain: In Vitro and In Vivo Evaluation.

ABSTRACT: Nucleotide-binding domain leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome complex regulates the caspase-1 activity and subsequent processing of interleukin-1β (IL-1β). Various inflammatory diseases involve the activation of inflammasome complexes; thus, the intervention in complex formation via small molecules offers a new therapeutic opportunity. The structure-guided design and synthesis of a series of methoxystilbenes and methoxy-2-phenylnaphthalenes identified new inhibitors of NLRP3 inflammasome complex. The tetramethoxystilbene 4o and trimethoxy 2-phenylnaphthalene 1t inhibit the release of a mature form of IL-1β in J774A.1 cells with IC₅₀ values of 1.39 and 2.07 μM, respectively. Mechanistic investigation revealed that tetramethoxyst

SUBMITTER: Abdullaha M 

PROVIDER: S-EPMC8369685 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature