Fig. 4: Schematic illustration of the mechanism of NLRP3 inhibitors tested via in vitro and in vivo experimental models.
From: Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors
Several molecules have shown inhibitory effects on NLRP3 activation, few of which have been validated in animal models. CY-09 and OLT1177 can inhibit the ATPase activity of the NACHT domain of NLRP3, which is critical for NLRP3 oligomerization. MCC950 is a compound that specifically inhibits NLRP3 inflammasome activation, but its molecular mechanism has not been fully elucidated. Tranilast directly binds to the NACHT domain of NLRP3 to inhibit NLRP3–NLRP3 interaction and the subsequent ASC oligomerization. Oridonin binds to cysteine 279 of NACHT via covalent bond formation to prevent NEK7–NLRP3 interaction and the subsequent NLRP3 inflammasome activation
