Benzarone

Benzarone is an oral inhibitor of human urate transporter 1 (hURAT1) with an IC₅₀ value of 2.8 μM, and it also acts as an uncoupler of oxidative phosphorylation. Benzarone can cause liver damage and promote cell apoptosis and necrosis. Benzarone can be used to lower serum uric acid levels and for research in vascular diseases^[1][2][3]. IC50 & Target:IC50: 2.8 μM (hURAT1 in oocyte)^[1] In Vitro: Benzarone (10-100 μM, 1 h) causes a reduction in mitochondrial membrane potential in isolated rat liver cells, decreases the oxidative status of L-glutamate and the respiration control ratio in rat liver mitochondria, and also leads to uncoupling of oxidative phosphorylation and a reduction in β-oxidation^[2].
Benzarone (1 nM-100 μM, 1 h) increases the production of reactive oxygen species, causes leakage of cytochrome C from HepG2 cell mitochondria, and induces permeability transition in rat liver mitochondria along with apoptosis and necrosis in rat liver cells^[2]. In Vivo: Benzarone (0.5 mg/kg, taken orally, single dose) reaches a peak plasma concentration of 0.96 pg equivalent/mL in dogs one hour after administration. The area under the plasma concentration-time curve (AUC_0-120h) is 43 pg equivalent h/mL, which is similar to the 3.8 pg equivalent•h/mL after intravenous administration, and binding reactions occur rapidly^[3].
Benzarone (2 mg/kg, given by gavage, single dose) is excreted in bile in rats, undergoes metabolism through direct conjugation, and exhibits enterohepatic recirculation^[3].