Details of the Drug

General Information of Drug (ID: DMDEXQ0)

Drug Name

Febuxostat

Synonyms

Adenuric; TEI; Uloric; Febuxostat [USAN]; S1547; TMX 67; Tei 6720; TMX-67; Tei-6720; Uloric (TN); Febuxostat (JAN/USAN/INN); TMX-67, Adenuric, Uloric, Febuxostat; 111GE013; 2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC ACID; 2-(3-Cyano-4-(2-methylpropoxy)phenyl)-4-methylthiazole-5-carboxylic acid;2-(3-Cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid; 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

316.4

Logarithm of the Partition Coefficient (xlogp)

3.9

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

6

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.6 +/- 0.6 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-1.5 h [2]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance: The total clearance of drug is 10-12 L/h [2]
Elimination: Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 8 hours [4]
Metabolism: The drug is metabolized via the liver [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.61228 micromolar/kg/day [5]
Vd: The volume of distribution (Vd) of drug is 29-75 L [6]
Water Solubility: The ability of drug to dissolve in water is measured as 0.013 mg/mL [3]

Chemical Identifiers

Formula: C16H16N2O3S
IUPAC Name: 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
Canonical SMILES: CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)O
InChI: InChI=1S/C16H16N2O3S/c1-9(2)8-21-13-5-4-11(6-12(13)7-17)15-18-10(3)14(22-15)16(19)20/h4-6,9H,8H2,1-3H3,(H,19,20)
InChIKey: BQSJTQLCZDPROO-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 134018
ChEBI ID: CHEBI:31596
CAS Number: 144060-53-7
DrugBank ID: DB04854
TTD ID: D0A5SE
INTEDE ID: DR0681
ACDINA ID: D00265

Combinatorial Drugs (CBD)

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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	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)_{Main DME}	DEYGVN4	UD11_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[9]
Dual specificity protein phosphatase 10 (DUSP10)	OTNG467B	DUS10_HUMAN	Gene/Protein Processing	[10]
Dual specificity protein phosphatase 4 (DUSP4)	OT6WAO12	DUS4_HUMAN	Gene/Protein Processing	[10]
Dual specificity protein phosphatase 5 (DUSP5)	OTH96RA7	DUS5_HUMAN	Gene/Protein Processing	[10]
Dual specificity protein phosphatase 8 (DUSP8)	OTPLMPG9	DUS8_HUMAN	Gene/Protein Processing	[10]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Gene/Protein Processing	[10]
Interleukin-1 receptor accessory protein (IL1RAP)	OTEU321R	IL1AP_HUMAN	Gene/Protein Processing	[10]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Post-Translational Modifications	[10]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1)	OTGP6GA4	NR4A1_HUMAN	Gene/Protein Processing	[10]
Ras-related protein M-Ras (MRAS)	OTNCVCQW	RASM_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Febuxostat (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[11]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[12]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[13]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Cannabidiol.	Epileptic encephalopathy [8A62]	[14]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[15]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[16]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[17]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Febuxostat and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[18]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[19]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Idelalisib.	Mature B-cell leukaemia [2A82]	[20]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Febuxostat and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[14]
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⏷ Show the Full List of 11 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Febuxostat 40 mg tablet	40 mg	Oral Tablet	Oral
Febuxostat 80 mg tablet	80 mg	Oral Tablet	Oral

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6817).
2	Hu M, Tomlinson B: Febuxostat in the management of hyperuricemia and chronic gout: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1209-20. doi: 10.2147/tcrm.s3310.
3	BDDCS applied to over 900 drugs
4	FDA Approved Products: Uloric (febuxostat) oral tablets
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Grabowski BA, Khosravan R, Vernillet L, Mulford DJ: Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects. J Clin Pharmacol. 2011 Feb;51(2):189-201. doi: 10.1177/0091270010365549. Epub 2010 Mar 30.
7	Clinical pipeline report, company report or official report of Takeda (2009).
8	In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica. 2008 May;38(5):496-510.
9	Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells. J Appl Toxicol. 2016 Sep;36(9):1120-8. doi: 10.1002/jat.3272. Epub 2015 Dec 7.
10	Febuxostat Increases Ventricular Arrhythmogenesis Through Calcium Handling Dysregulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Toxicol Sci. 2022 Sep 24;189(2):216-224. doi: 10.1093/toxsci/kfac073.
11	Cerner Multum, Inc. "Australian Product Information.".
12	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
13	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
14	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
16	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
17	Canadian Pharmacists Association.
18	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
19	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
20	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.