Topiroxostat

• CAT Number: I004155
• CAS Number: 577778-58-6
• Molecular Formula: C13H8N6
• Molecular Weight: 248.2
• Purity: ≥95%
• Synonyms: 4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile
• Target: XAO
• Solubility: DMSO: ≤ 23.5 mg/mL
• Storage: Store at -20C
• IC50: 5.3 nM [1]
• InChI: InChI=1S/C13H8N6/c14-8-11-7-10(3-6-16-11)13-17-12(18-19-13)9-1-4-15-5-2-9/h1-7H,(H,17,18,19)
• InChIKey: UBVZQGOVTLIHLH-UHFFFAOYSA-N
• SMILES: C1=CN=CC=C1C2=NC(=NN2)C3=CC(=NC=C3)C#N

Topiroxostat (CAT: I004155) is a xanthine oxidase inhibitor used for the treatment of hyperuricemia in patients with gout. It works by inhibiting the enzyme xanthine oxidase, which is involved in the production of uric acid. By reducing uric acid levels, topiroxostat helps prevent the formation of urate crystals and reduces the risk of gout attacks. It is a selective and reversible inhibitor of xanthine oxidase and has shown efficacy in lowering serum uric acid levels in clinical trials. Topiroxostat provides an alternative treatment option for patients with gout who may not tolerate or respond adequately to other available medications.

Overview of Clinical Research

Topiroxostat is an Xanthine dehydrogenase inhibitor and  Xanthine oxidase inhibitor. It has been granted for the new molecular entity.

Reference

1:Effect of switching xanthine oxidoreductase inhibitor from febuxostat to topiroxostat on urinary protein excretion. Terawaki H, Hoshi H, Kazama JJ.Clin Exp Nephrol. 2017 Apr;21(2):356-357. doi: 10.1007/s10157-017-1388-7. Epub 2017 Feb 28. No abstract available. PMID: 28247173
2:Clinical Effects of Topiroxostat on Renal and Endothelial Function in A Patient with Chronic Kidney Disease and Hyperuricemic Arteriolopathy: A Case Report. Tanaka A, Nakamura T, Sato E, Node K.Drugs R D. 2017 Mar;17(1):97-101. doi: 10.1007/s40268-016-0169-1. PMID: 28074335 Free PMC Article
3:Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study. Hosoya T, Sasaki T, Ohashi T.Clin Rheumatol. 2017 Mar;36(3):649-656. doi: 10.1007/s10067-016-3474-8. Epub 2016 Nov 10. PMID: 27832384 Free PMC Article
4:Randomized control trial for the assessment of the anti-albuminuric effects of topiroxostat in hyperuricemic patients with diabetic nephropathy (the ETUDE study). Kato S, Ando M, Mizukoshi T, Nagata T, Katsuno T, Kosugi T, Tsuboi N, Maruyama S.Nagoya J Med Sci. 2016 May;78(2):135-42. PMID: 27303100 Free PMC Article
5:Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study. Hosoya T, Ogawa Y, Hashimoto H, Ohashi T, Sakamoto R.J Clin Pharm Ther. 2016 Jun;41(3):290-7. doi: 10.1111/jcpt.12391. Epub 2016 Apr 24. PMID: 27109450
6:Clinical efficacy and safety of topiroxostat in Japanese male hyperuricemic patients with or without gout: an exploratory, phase 2a, multicentre, randomized, double-blind, placebo-controlled study. Hosoya T, Sasaki T, Hashimoto H, Sakamoto R, Ohashi T.J Clin Pharm Ther. 2016 Jun;41(3):298-305. doi: 10.1111/jcpt.12392. Epub 2016 Apr 15. PMID: 27079434
7:Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. Nakamura T, Murase T, Nampei M, Morimoto N, Ashizawa N, Iwanaga T, Sakamoto R.Eur J Pharmacol. 2016 Jun 5;780:224-31. doi: 10.1016/j.ejphar.2016.03.055. Epub 2016 Mar 30. PMID: 27038523
8:Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury. Kamijo-Ikemori A, Sugaya T, Hibi C, Nakamura T, Murase T, Oikawa T, Hoshino S, Hisamichi M, Hirata K, Kimura K, Shibagaki Y.Am J Physiol Renal Physiol. 2016 Jun 1;310(11):F1366-76. doi: 10.1152/ajprenal.00517.2015. Epub 2016 Mar 30. PMID: 27029427
9:Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel xanthine oxidoreductase inhibitor. Taniguchi T, Ashizawa N, Matsumoto K, Iwanaga T, Saitoh K.J Pharm Pharmacol. 2016 Jan;68(1):76-83. doi: 10.1111/jphp.12490. Epub 2015 Nov 21. PMID: 26589240
10:Apoptosis induced by an uromodulin mutant C112Y and its suppression by topiroxostat. Utami SB, Mahati E, Li P, Maharani N, Ikeda N, Bahrudin U, Munemura C, Hosoyamada M, Yamamoto Y, Yoshida A, Nakayama Y, Higaki K, Nanba E, Ninomiya H, Shirayoshi Y, Ichida K, Yamamoto K, Hosoya T, Hisatome I.Clin Exp Nephrol. 2015 Aug;19(4):576-84. doi: 10.1007/s10157-014-1032-8. Epub 2014 Sep 20. PMID: 25239792