Cyclofenil blocks the secretion of IL-1β by inhibiting assembly of the NLRP3 inflammasome independent of estrogen receptor.

Cyclofenil is a modulator of estrogen receptor and is used clinically as an ovulation-inducing drug with antiviral activity. However, the mechanism by which cyclofenil works without estrogen receptor remains unknown. In this study, we screened for a small-molecule drug targeting the NLRP3 inflammasome and found that cyclofenil inhibited the secretion of IL-1β in a dose-dependent manner. Intriguingly, cyclofenil impedes activation of the NLRP3 inflammasome, independent of estrogen receptor, without interfering with the priming stage. Additionally, cyclofenil blocks ASC oligomerization and pyroptosis, preventing maturation of IL-1β and caspase-1. This study offers new evidence that cyclofenil is an anti-inflammatory drug and may be a novel clinical option for NLRP3 inflammasome-related diseases.