Topiroxostat  (Synonyms: FYX-051)

Topiroxostat (FYX-051) is a potent and orally active xanthine oxidoreductase (XOR) inhibitor with an IC₅₀ value of 5.3 nM and a K_i value of 5.7 nM. Topiroxostat exhibits weak CYP3A4-inhibitory activity (18.6%). Topiroxostat has the potential for hyperuricemia treatment^[1][2].

IC50: 5.3 nM (XOR)^[1]
Ki: 5.7 nM (XOR)^[2]

These potent and more sustained effects of Topiroxostat (FYX-051, compound 39) have been confirmed by a crystallographic analysis of XOR-Topiroxostat complex. The cyano group of Topiroxostat has been reported to play an important role in the binding activity between Topiroxostat and XOR. This is attributable to the formation of a hydrogen bond between Asn 768 of XOR and the cyano group of Topiroxostat^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Topiroxostat (FYX-051; 0.03-10 mg/kg; oral administration; for 1 hour; male Wistar/ST strain rats) treatment shows a potent and long-lasting hypouricemic effect in a rat model of potassium oxonate-induced hyperuricemia^[2] .
The C_max and bioavailability of Topiroxostat (FYX-051, compound 39) are as high as 4.62 μg/mL (3 mg/kg) and 69.6%, respectively. Moreover, the t_1/2 value of Topiroxostat is 19.7 hours^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

248.24

Solid

C₁₃H₈N₆

577778-58-6

N#CC1=NC=CC(C2=NNC(C3=CC=NC=C3)=N2)=C1

Room temperature in continental US; may vary elsewhere.

• [1]. Sato T, et al. Discovery of 3-(2-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051 - a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia [corrected]. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6225-9.  [Content Brief]

  [2]. Matsumoto K, et al. FYX-051: a novel and potent hybrid-type inhibitor of xanthine oxidoreductase. J Pharmacol Exp Ther. 2011 Jan;336(1):95-103.  [Content Brief]