Febuxostat sodium

Febuxostat (TEI 6720) sodium is a potent, selective and non-purine xanthine oxidase (XO) inhibitor with a Ki value of 0.6 nM. Febuxostat sodium has the potential for the research of hyperuricemia and gout[1][2][3].

Research Areas >> Cardiovascular Disease

Research Areas >> Metabolic Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Xanthine Oxidase

Febuxostat sodium displays potent mixed-type inhibition of the activity of purified bovine milk xanthine oxidase, with Ki and Ki' values of 0.6 nM and 3.1 nM respectively, indicating inhibition of both the oxidized and reduced forms of xanthine oxidase[1].

Febuxostat sodium (5-6 mg/kg; i.e.; daily for 4 weeks) (fed a high-fructose diet (60% fructose) for 8 wk) significantly reduces lomerular pressure, renal vasoconstriction, and afferent arteriolar area relative to fructose+P rats, and shows no significant effects in rats on a normal diet when febuxostat treatment alone[2]. Febuxostat sodium (3-4 mg/kg; p.o.; daily for 4 weeks) with oxonic acid (750 mg/kg; oral gavage; daily for 4 weeks) preventes renal injury in 5/6 Nx (5/6 nephrectomy) rats with and without coexisting hyperuricemia[3]. Febuxostat sodium (2.5 mg/kg; p.o.; daily for 12 weeks) inhibits plaque formation in ApoE−/− mice and reduces the levels of ROS in the aortic wall of atherosclerotic mice[4]. Febuxostat sodium (15.6 mg/kg; p.o.; once daily for 21 successive days) shows antidepressant effect by significantly reduces the immobility time in the FST in mouse[5]. Febuxostat sodium (10 mg/kg; p.o.; daily for 21 days) administration with doxorubicin caused a significant decrease in nephrotoxicity markers and inflammatory mediators, restoration of normal values of oxidative stress biomarkers and hampering the expression of renal caspase-3[6].

[1]. Takano Y, et al. Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase. Life Sci, 2005, 76(16), 1835-1847.

[2]. Sanchez-Lozada LG, et al. Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol Renal Physiol, 2008, 294(4), F710-F718.

[3]. Sanchez-Lozada LG, et al. Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia. Nephron Physiol, 2008, 108(4), p69-p78.

[4]. Nomura J, et al. Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice. Sci Rep. 2014 Apr 1;4:4554.

[5]. Karve AV, et al. Evaluation of effect of allopurinol and febuxostat in behavioral model of depression in mice. Indian J Pharmacol. 2013 May-Jun;45(3):244-7.

[6]. Khames A, et al. Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats. Eur J Pharmacol. 2017 Jun 15;805:118-124.