NLRP3-IN-76 is an orally active NLRP3 inhibitor that suppresses the production of NO and reduces the mRNA levels of pro-inflammatory cytokines (iNOS, IL-6, IL-1β, and TNFα). It exerts anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome and the NF-κB signaling pathway. Furthermore, NLRP3-IN-76 can ameliorate DSS-induced colitis and is applicable for studying inflammatory bowel disease (IBD).

NLRP3-IN-76 (Compound ST12) at a concentration of 10 μM for 24 hours reduces nitric oxide (NO) production by 52.67% in LPS-induced RAW264.7 cells. Additionally, NLRP3-IN-76 suppresses the mRNA levels of pro-inflammatory cytokines, such as inducible nitric oxide synthase (iNOS), IL-6, IL-1β, and TNF-α, in LPS-stimulated RAW264.7 cells. Furthermore, when used at concentrations ranging from 2.5 to 10 μM for 24 hours, NLRP3-IN-76 inhibits NLRP3 inflammasome activation and NF-κB signaling pathway activation in LPS-stimulated RAW264.7 cells.

NLRP3-IN-76 (Compound ST12) (35 mg/kg, administered via gavage for 9 days) safeguards mice from DSS-induced colitis by inhibiting the in vivo activation of the NLRP3 inflammasome. Additionally, NLRP3-IN-76 (100-400 mg/kg, orally) is well-tolerated in C57 mice, with an LD50 of 300 mg/kg.