Topiroxostat

Description: Topiroxostat (formerly known as FYX-051; Brand names: Topiloric and Uriadec) is a novel and potent xanthine oxidoreductase (XOR) inhibitor which reduces serum urate levels and has IC50 value of 5.3 nM for XOR. It is a approved drug for the treatment of gout and hyperuricemia. It was initially approved in Japan in June 2013. Steady-state kinetics study showed that it initially behaved as a competitive-type inhibitor with a K(i) value of 5.7 x 10(-9) M, then after a few minutes it formed a tight complex with XOR via a Mo-oxygen-carbon atom covalent linkage, as reported previously (Proc Natl Acad Sci USA 101:7931-7936, 2004). Thus, FYX-051 is a hybrid-type inhibitor exhibiting both structure- and mechanism-based inhibition. The FYX-051-XOR complex decomposed with a half-life of 20.4 h, but the enzyme activity did not fully recover.

References: J Pharmacol Exp Ther. 2011 Jan; 336(1):95-103.