CIAC101 is an effective TLR4 inhibitor that can cross the blood-brain barrier, with an IC50 of 17.0 nM. It blocks Lipopolysaccharides (LPS)-induced NF-κB activation and reduces the expression of pro-inflammatory mediators (iNOS, IL-1β, TNF-α, and IL-6). CIAC101 exhibits potent anti-neuroinflammatory activity and counters drug-induced neurobehavioral adaptations, making it useful for research on addiction and neurological disorders.

TLR4:17 nM

CIAC101 inhibits the excessive production of NO triggered by Lipopolysaccharides (LPS) in BV-2 microglial cells, with an IC50 of 17 nM. CIAC101 (0.1 nM-10 μM; 24 h) also dose-dependently suppresses LPS-induced NF-κB activation (IC50 of 65.5 nM) and reduces the expression of pro-inflammatory mediators in HEK-BluehTLR4 cells. It demonstrates no significant cytotoxicity. In the BV-2 NF-κB luciferase reporter cell line, CIAC101 (0.1 nM-10 μM; 24 h) exhibits dose-dependent inhibition of LPS-induced NF-κB activation without apparent cytotoxicity, with an IC50 of 90.2 nM. Additionally, in LPS-stimulated BV-2 microglial cell models, CIAC101 (0.01-1 μM; 24 h) reduces the mRNA expression of LPS-induced iNOS, IL-1β, TNF-α, and IL-6 in a concentration-dependent manner.

CIAC101, administered intraperitoneally at doses of 0.005-0.2 mg/kg from day 4 to day 10, effectively counters methamphetamine (METH)-induced neurobehavioral adaptations and neuroinflammation in Balb/c mice. A dosage of 20 mg/kg, given intraperitoneally once daily for 14 days, is well tolerated in Balb/c mice, showing no signs of acute systemic or organ toxicity.