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Topiroxostat

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Chemical Structure| 577778-58-6 同义名 : 托比司他 ;FYX-051
CAS号 : 577778-58-6
货号 : A119678
分子式 : C13H8N6
纯度 : 98%
分子量 : 248.243
MDL号 : MFCD17167057
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(80.57 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.03mL

0.81mL

0.40mL

20.14mL

4.03mL

2.01mL

40.28mL

8.06mL

4.03mL
参考文献

[1]Sato T, Ashizawa N, 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.

[2]Omura K, Nakazawa T, et al. Characterization of N-glucuronidation of 4-(5-pyridin-4-yl-1H-[1,2,4] triazol-3-yl) pyridine-2-carbonitrile (FYX-051): a new xanthine oxidoreductase inhibitor. Drug Metab Dispos. 2007 Dec;35(12):2143-8.

[3]Sato T, Ashizawa N, Matsumoto K, Iwanaga T, Nakamura H, Inoue T, Nagata O. 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. doi: 10.1016/j.bmcl.2009.08.091. Epub 2009 Sep 2. Erratum in: Bioorg Med Chem Lett. 2010 Apr 1;20(7):2390. PMID: 19783139.

[4]Matsumoto K, Okamoto K, Ashizawa N, Nishino T. FYX-051: a novel and potent hybrid-type inhibitor of xanthine oxidoreductase. J Pharmacol Exp Ther. 2011 Jan;336(1):95-103. doi: 10.1124/jpet.110.174540. Epub 2010 Oct 15. PMID: 20952484.

[5]Nakamura T, Murase T, Nampei M, Morimoto N, Ashizawa N, Iwanaga T, Sakamoto R. Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. Eur J Pharmacol. 2016 Jun 5;780:224-31. doi: 10.1016/j.ejphar.2016.03.055. Epub 2016 Mar 30. PMID: 27038523.