Xanthine oxidoreductase (XOR) belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. Xanthine oxidoreductase is a key enzyme in purine degradation. It catalyzes the oxidation of hypoxanthine to xanthine and the oxidation of xanthine to uric acid. Xanthine oxidoreductase contributes to the generation of reactive oxygen species.
Topiroxostat, also termed FYX-051, is a XOR inhibitor with IC50 value of 5.3 nM in an in vitro assay[3]. Steady-state kinetics study showed that topiroxostat behaved as a competitive-type inhibitor with a Ki value of 5.7 × 10 nM[4].
Oral administration of Topiroxostat at doses ranging in 0.03-1mg/kg dose-dependently decreased serum urate levels in oxonate-induced hyperuricemic rats, with ED50 values of 0.15 mg/kg, 0.25 mg/kg and 0.70 mg/kg at 1h, 6h, and 12h[4]. Oral administration of Topiroxostat at doses of 0.1, 0.3, 1 and 3 mg/kg/day for 4 weeks dose-dependently decreased the urinary albumin excretion, inhibited plasma XOR activity in diabetic mice model[5].
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