Details of the Drug

General Information of Drug (ID: DMA04DE)

Drug Name

Topiroxostat

Synonyms

FYX-051; Xanthine oxidoreductase inhibitor (oral, gout), Fuji Yakuhin

Indication

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

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

248.24

Logarithm of the Partition Coefficient (xlogp)

1.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 1319 +/- 162 mcgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 413 +/- 77 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.5-6 h [2]
Clearance: The renal clearance of drug is 17.4 mL/h [3]
Elimination: Urinary excretion and fecal excretion of radiolabeled topiroxostat are 30.4% and 40.9% of total dose of 1mg/kg administered to rats, respectively [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 hours [3]
Metabolism: The drug is metabolized via the hepatic metabolism [5]

Chemical Identifiers

Formula: C13H8N6
IUPAC Name: 4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile
Canonical SMILES: C1=CN=CC=C1C2=NC(=NN2)C3=CC(=NC=C3)C#N
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

Cross-matching ID

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	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A9 (UGT1A9)_{Main DME}	DE85D2P	UD19_HUMAN	Substrate	[7]

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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This Drug

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	Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. Cancer Chemother Pharmacol. 2012 Mar;69(3):789-97. doi: 10.1007/s00280-011-1760-3. Epub 2011 Oct 29.
3	Pharmaceuticals and Medical Devices Agency (PMDA): Topiroxostat review
4	Nakazawa T, Miyata K, Omura K, Iwanaga T, Nagata O: Metabolic profile of FYX-051 (4-(5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl)pyridine-2-carbonitrile) in the rat, dog, monkey, and human: identification of N-glucuronides and N-glucosides. Drug Metab Dispos. 2006 Nov;34(11):1880-6. Epub 2006 Aug 16.
5	Kamdem LK, Liu Y, Stearns V, Kadlubar SA, Ramirez J, Jeter S, Shahverdi K, Ward BA, Ogburn E, Ratain MJ, Flockhart DA, Desta Z: In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69. doi: 10.1111/j.1365-2125.2010.03791.x.
6	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.
7	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.