Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMA04DE)

• Drug Name: Topiroxostat Drug Info
• Synonyms: FYX-051; Xanthine oxidoreductase inhibitor (oral, gout), Fuji Yakuhin

Indication

Disease Entry	ICD 11	Status	REF
Gout	FA25	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 5288320
  CAS Number: CAS 577778-58-6
  TTD Drug ID: DMA04DE
  INTEDE Drug ID: DR1619

Molecule-Related Drug Atlas

Drug(s) Targeting Xanthine dehydrogenase/oxidase (XDH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopurinol	DMLPAOB	Gout	FA25	Approved	[4]
Febuxostat	DMDEXQ0	Hyperuricaemia	5C55.Y	Approved	[5]
Fosdenopterin	DMR0TYK	Molybdenum cofactor deficiency	5B5K.A	Approved	[6]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
Oxypurinol	DMURH4X	Heart failure	BD10-BD13	Phase 2/3	[8]
BAICALEIN	DM4C7E6	Influenza virus infection	1E30-1E32	Phase 2	[9]
TMX-049	DME8PFQ	Diabetic nephropathy	GB61.Z	Phase 2	[10]
LC-350189	DMHT3CB	Gout	FA25	Phase 1	[11]
Azaindole derivative 5	DMD2BL3	N. A.	N. A.	Patented	[12]
Fused heterocyclic compound 3	DM2QVHY	N. A.	N. A.	Patented	[12]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A9 (UGT1A9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[13]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[17]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[16]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[16]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[18]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[16]
Haloperidol	DM96SE0	Delirium		Approved	[16]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A9 (UGT1A9) Main DME	DE85D2P	UD19_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT02327754) Effect of Topiroxostat on Urinary Albumin Excretion Early Stage Diabetic Nephropathy and Hyperuricemia With or Without Gout. U.S. National Institutes of Health.
• [2] QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52.
• [3] 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.
• [4] Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
• [5] Clinical pipeline report, company report or official report of Takeda (2009).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [7] Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
• [8] Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
• [9] Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
• [10] Clinical pipeline report, company report or official report of Teijin Pharma.
• [11] Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
• [12] An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345.
• [13] Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
• [14] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [15] Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
• [16] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [17] The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
• [18] The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.