NF-κB-IN-4 (compound 17) is a potent inhibitor of the NF-κB pathway that can cross the blood-brain barrier (BBB). It exhibits potential anti-neuroinflammatory activity with low toxicity, making it suitable for researching neuroinflammation-related diseases. NF-κB-IN-4 can block IκBα activation and phosphorylation, reduce NLRP3 expression, and thereby inhibit NF-κB activation [1].

NF-κB-IN-4 (compound 17), at concentrations of 0-10 μM over 24 hours, exhibits potent anti-inflammatory effects. At 0-5 μM, it significantly reduces LPS-induced p-IκBα levels, inhibits IκBα phosphorylation, and decreases NLRP3, ASC, and caspase-1 protein expression in BV2 microglial cells. NF-κB-IN-4 induces dose-dependent apoptosis following LPS exposure. In cytotoxicity assays, it demonstrates high anti-inflammatory activity with 97.4% cell survival and inhibition of TNF-α and IL-6 release by 60.8% and 80.2%, respectively, at concentrations of 0, 2.5, 5, and 10 μM. Western blot analyses confirm these significant effects at 0, 1.25, 2.5, and 5 μM. Apoptosis rates are 30.7% at 2.5 μM and 13.0% at 5 μM.