Benzarone (Synonyms: L 2197, NSC 82134)

Benzarone is an active metabolite of the urate anion transporter 1 (URAT1) inhibitor benzbromarone .^1,2 It inhibits URAT1 in Xenopus oocytes expressing the human enzyme (IC₅₀ = 2.8 µM).² Benzarone also inhibits the tyrosine phosphatase activity of eyes absent homolog 3 (EYA3; IC₅₀ = 17.5 µM), as well as reduces the proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 7.5 µM.³ It uncouples oxidative phosphorylation in isolated rat liver mitochondria and induces apoptosis and necrosis in isolated rat hepatocytes.⁴ Benzarone (25 µg/g) reduces tumor growth in an A-673 Ewing sarcoma mouse xenograft model.⁵

1.StÜber, W., and MÖller, H.Determination of benzbromarone, bromobenzarone and benzarone in plasma by gas chromatography—mass spectrometryJ. Chromatogr. B Biomed. Sci. Appl.224(2)327-331(1981) 2.Wempe, M.F., Jutabha, P., Quade, B., et al.Developing potent human uric acid transporter 1 (hURAT1) inhibitorsJ. Med. Chem.54(8)2701-2713(2011) 3.Pandey, R.N., Wang, T.S., Tadjuidje, E., et al.Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agentsPLoS One8(12)e84582(2013) 4.Kaufmann, P., TÖrÖk, M., HÄnni, A., et al.Mechanisms of benzarone and benzbromarone-induced hepatic toxicityHepatology41(4)925-935(2005) 5.Wang, Y., Pandey, R.N., Roychoudhury, K., et al.Targeting EYA3 in ewing sarcoma retards tumor growth and angiogenesisMol. Cancer Ther.20(5)803-815(2021)