Febuxostat

Febuxostat (TEI 6720) is selective xanthine oxidase inhibitor with a K_i of 0.6 nM^[1]. IC50 & Target: Ki: 0.6 nM (Xanthine oxidase)^[1] In Vitro: Febuxostat displays potent mixed-type inhibition of the activity of purified bovine milk xanthine oxidase, with K_i and K_i' values of 0.6 nM and 3.1 nM respectively, indicating inhibition of both the oxidized and reduced forms of xanthine oxidase^[1]. In Vivo: Febuxostat (5-6 mg/kg/day) combined with fructose significantly lowers blood pressure, UA, triglycerides, and insulin in rats compared with fructose alone. Febuxostat (5–6 mg/kg/day) combined with fructose also reduces glomerular pressure, renal vasoconstriction, and afferent arteriolar area in rats compared with fructose alone^[2].
Febuxostat prevents hyperuricemia in 5/6 nephrectomy (5/6 Nx)+oxonic acid (OA)+Febuxostat(Fx) rats and ameliorates proteinuria, preserves renal function and prevents glomerular hypertension in both 5/6 nephrectomy (5/6 Nx)+vehicle (V)+Febuxostat(Fx) and 5/6 nephrectomy (5/6 Nx)+oxonic acid (OA)+Febuxostat(Fx) groups^[3].
Febuxostat (5 mg/kg/d by gavage for 8 days) treatment after transverse aortic constriction (TAC) attenuates the TAC-induced left ventricular (LV) hypertrophy and dysfunction. Febuxostat blunts the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-Erk(Thr202/Tyr204), and p-mTOR(Ser2488), with no effect on total Erk or total mTOR^[4].