Carbenoxolone

Carbenoxolone is a blood-brain barrier-permeable Pannexin1 inhibitor, gap junction (Gap junction) blocker, and β-amyloid 42 inhibitor. Carbenoxolone modulates voltage-gated currents of wild-type and mutant Panx1, and inhibits stimulus-activated Panx1 channel function. Carbenoxolone interacts with stable residues of β-amyloid 42 peptides, fibrils and oligomers, thereby inhibiting their aggregation. Carbenoxolone alleviates liver fibrosis. Carbenoxolone exerts neuroprotective and nootropic effects. Carbenoxolone can be used in studies related to Alzheimer's disease and liver fibrosis^[1][2][3][4]. In Vitro:Carbenoxolone (0.01-1000 μM) potently inhibits voltage-gated wild-type human Pannexin1 channel activity in HEK293 cells with an IC₅₀ of ~2 μM, with greater inhibition (up to ~90% at 100 mV) observed in strongly rectifying cell populations^[1].
Carbenoxolone (0.01-1000 μM) potentiates voltage-gated hPanx1/Panx3 loop1 chimera channel activity in HEK293 cells with an EC₅₀ of ~120 μM, producing a nearly fourfold increase in current at a saturating concentration of 562 μM^[1].
Carbenoxolone (50-100 μM; 4 days) inhibits amyloid-beta 42 peptide aggregation in a concentration-dependent manner, with 22.54% inhibition at 50 μM and 47.16% inhibition at 100 μM following 4-day incubation at 37 °C^[2].
Carbenoxolone (50 μM; 24-48 h) inhibits gap junction activity in primary rat hepatocytes^[3]. In Vivo:Carbenoxolone (1 mg/kg body weight/day; administered via an osmoti pump implanted in the peritoneal cavity; 14 days)reduces liver fibrosis and hepatic stellate cell activation in TAA-induced fibrotic mice, while modulating hepatic inflammatory protein levels and glutathione peroxidase activity^[3].