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Details

Stereochemistry ACHIRAL
Molecular Formula C16H16N2O3S
Molecular Weight 316.3765
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEBUXOSTAT

SMILES

CC(C)COc1ccc(cc1C#N)-c2nc(C)c(C(=O)O)s2

InChI

InChIKey=BQSJTQLCZDPROO-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
Molecular Formula C16H16N2O3S
Molecular Weight 316.3765
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/uloric.html

Febuxostat (ULORIC) is a novel, xanthine oxidase/dehydrogenase (XO/XDH) inhibitor being developed by Teijin, TAP Pharmaceuticals, and Ipsen for the treatment of gout. The currently available XO inhibitor, allopurinol, has been associated with serious instances of severe hypersensitivity, in some cases leading to fatalities. There is some suggestion that febuxostat is less prone to excacerbate systemic inflammatory events in animal studies. Febuxostat, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. Febuxostat is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations. Febuxostat is used for the treatment of hyperuricemia in patients with gout.

Originator

Approval Year

2009
32
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
3315
 1.26 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
4033
Uloric

Approved Use

Uloric is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout.

Launch Date

1.23439677E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.53 μg/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16884320
40 mg 1 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FEBUXOSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3.98 μg × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16884320
40 mg 1 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FEBUXOSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.2 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16884320
40 mg 1 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FEBUXOSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16884320
40 mg 1 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FEBUXOSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
40 mg 1 times / day steady, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
unhealthy, adult
n = 757
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 757
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
Disc. AE: Function liver abnormal...
AEs leading to
discontinuation/dose reduction:
Function liver abnormal (1.8%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
unhealthy, adult
n = 1279
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 1279
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
Disc. AE: Function liver abnormal...
AEs leading to
discontinuation/dose reduction:
Function liver abnormal (1.2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Function liver abnormal 1.8%
Disc. AE
40 mg 1 times / day steady, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
unhealthy, adult
n = 757
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 757
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
Function liver abnormal 1.2%
Disc. AE
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
unhealthy, adult
n = 1279
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 1279
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021856lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
753
inducer
191

substrate
530

inhibitor
825
inhibitor
894

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
725

CYP2C19
700
CYP1A2
526

CYP2C8
354

CYP1A1
179

UGT1A1
198

UGT1A3
195

UGT1A9
180

UGT2B7
182

P-gp
724
CYP1A
31

CYP2B6
243

CYP2C19
145

CYP3A4/5
51
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A
63
 low
CYP2B6
465
 low
CYP2C19
738
 low
CYP2C9
851
 low
CYP3A4/5
142
 low
CYP2D6
908
 moderate [Ki 40 uM]
weak (co-administration study)
Comment: competitive inhibition; Administration with desipramine resulted in an increase in Cmax (16%) and AUC (22%) of desipramine
Page: 38,13
CYP1A2
805
 no [Ki >100 uM]
CYP2C19
738
 no [Ki >100 uM]
CYP2C9
851
 no [Ki >100 uM]
CYP3A4
920
 no [Ki >100 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
724
 inconclusive
CYP1A1
179
 yes
CYP1A2
526
 yes
CYP2C8
354
 yes
UGT1A1
198
 yes
UGT1A3
195
 yes
UGT1A9
180
 yes
UGT2B7
182
 yes
CYP2C9
530
 yes
no (co-administration study)
Comment: warfarin: no effect at steady-state
Page: 12,20,38
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:31596
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31596
ChemicalBook
CB22508843
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22508843
ChemicalBook
CB4841564
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4841564
MolPort
MolPort-005-940-740
https://www.molport.com/shop/molecule-link/MolPort-005-940-740
Selleck Chemicals
Febuxostat(Uloric)
http://www.selleckchem.com/products/Febuxostat(Uloric).html
ZINC
ZINC000000005423
http://zinc15.docking.org/substances/ZINC000000005423
eMolecules
6719182
https://www.emolecules.com/cgi-bin/more?vid=6719182
PubMed

PubMed

TitleDatePubMed
Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout.
2006 Dec
Hyperuricemia and gout: new insights into pathogenesis and treatment.
2007
Emerging therapies in the long-term management of hyperuricaemia and gout.
2007 Apr
Gateways to clinical trials.
2007 Dec
Assessment of outcome in clinical trials of gout--a review of current measures.
2007 Dec
Febuxostat: a novel non-purine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in gout.
2007 Feb
[Crystal-induced arthritis--old but important].
2007 Jul
Uricase and other novel agents for the management of patients with treatment-failure gout.
2007 Jun
Tumor lysis syndrome.
2007 Jun
Therapeutic advances in gout.
2007 Mar
Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout.
2007 Mar 2
Developments in the scientific and clinical understanding of gout.
2008
Febuxostat : a viewpoint by N. Lawrence Edwards.
2008
Febuxostat : a viewpoint by Naomi Schlesinger.
2008
Febuxostat: a viewpoint by H. Ralph Schumacher Jr and Lan X. Chen.
2008
Febuxostat.
2008
Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia.
2008
Gateways to clinical trials.
2008 Apr
[New antihyperuricemic medicine: febuxostat, Puricase, etc].
2008 Apr
[Inhibitors of xanthine oxidoreductase].
2008 Apr
Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome.
2008 Apr
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.
2008 Apr
Febuxostat in the management of hyperuricemia and chronic gout: a review.
2008 Dec
Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors: allopurinol, febuxostat, and FYX-051.
2008 Feb
Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.
2008 Jun
Refractory gout: what is it and what to do about it?
2008 Mar
Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects.
2008 Mar
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.
2008 May
Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice.
2008 Nov
Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.
2008 Nov 15
Gout management: let's get it right this time.
2008 Nov 15
Gateways to clinical trials.
2008 Oct
The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.
2008 Sep
The role of urate and xanthine oxidase in vascular oxidative stress: future directions.
2009
Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress.
2009
Febuxostat: new drug. Hyperuricaemia: risk of gout attacks.
2009 Apr
A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout.
2009 Apr
New gout treatment approved.
2009 Apr 1
Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates.
2009 Apr 16
Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.
2009 Feb
Gout Study Group: update on hyperuricemia and gout.
2009 Jul
Gout--what are the treatment options?
2009 Jun
Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.
2009 Jun
Update on emerging urate-lowering therapies.
2009 Mar
Febuxostat.
2009 Mar
New drugs: Febuxostat, lacosamide, and rufinamide.
2009 May-Jun
Approach to the treatment of hyperuricemia.
2009 Nov
Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.
2009 Oct
Update on gout and hyperuricemia.
2010 Feb
Update on gout: new therapeutic strategies and options.
2010 Jan
Patents

Patents

20060252808
1
20080038242
1
20080096904
1
20080145846
1

Sample Use Guides

In Vivo Use Guide
For treatment of hyperuricemia in patients with gout, the recommended dose is 40 mg or 80 mg once daily.
Route of Administration: Oral
In Vitro Use Guide
Febuxostat (200uM) inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:09:35 UTC 2021
Edited
by admin
on Fri Jun 25 22:09:35 UTC 2021
Record UNII
101V0R1N2E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FEBUXOSTAT
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
FEBUXOSTAT [VANDF]
Common Name English
TMX-67
Code English
NSC-758874
Code English
2-(3-CYANO-4-ISOBUTOXYPHENYL)-4-METHYL-1,3-THIAZOLE-5-CARBOXYLIC ACID
Systematic Name English
FEBUXOSTAT [USAN]
Common Name English
FEBUXOSTAT [MI]
Common Name English
FEBUXOSTAT [INN]
Common Name English
ADENURIC
Brand Name English
5-THIAZOLECARBOXYLIC ACID, 2-(3-CYANO-4-(2-METHYLPROPOXY)PHENYL)-4-METHYL-
Systematic Name English
FEBUXOSTAT [JAN]
Common Name English
FEBUXOSTAT [EMA EPAR]
Common Name English
FEBUXOSTAT [MART.]
Common Name English
FEBUXOSTAT [WHO-DD]
Common Name English
ULORIC
Brand Name English
FEBUXOSTAT [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
LIVERTOX 400
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
WHO-VATC QM04AA03
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
EMA ASSESSMENT REPORTS ADENURIC (AUTHORIZED: GOUT)
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
WHO-ATC M04AA03
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
NDF-RT N0000175698
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
NDF-RT N0000000206
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
NCI_THESAURUS C1637
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
NCI_THESAURUS C921
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
Code System Code Type Description
FDA UNII
101V0R1N2E
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
DRUG BANK
DB04854
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
NCI_THESAURUS
C65629
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
MESH
C084623
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
EVMPD
SUB25382
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
DRUG CENTRAL
1137
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
INN
8140
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
EPA CompTox
144060-53-7
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
RXCUI
73689
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M5253
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1164729
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
IUPHAR
6817
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
CAS
144060-53-7
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
PUBCHEM
134018
Created by admin on Fri Jun 25 22:09:35 UTC 2021 , Edited by admin on Fri Jun 25 22:09:35 UTC 2021
PRIMARY
Related Record Type Details
Structure of FEBUXOSTAT
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Structure of FEBUXOSTAT
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B7
METABOLIC ENZYME -> SUBSTRATE
XANTHINE DEHYDROGENASE/OXIDASE
TARGET -> INHIBITOR
Ki
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C9
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2D6
METABOLIC ENZYME -> INHIBITOR
Ki
CYTOCHROME P450 1A1
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
Structure of FEBUXOSTAT HEMIHYDRATE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of 2-(3-CYANO-4-HYDROXYPHENYL)-4-METHYL-5-THIAZOLECARBOXYLIC ACID
METABOLITE -> PARENT
67M-3, a major metabolite formed in vitro, was not detected in significant amount in vivo. 67M-3 was mainly metabolized by CYP1A1, whose level is low in healthy non-smoking
Structure of 2-(4-(2-CARBOXYPROPOXY)-3-CYANOPHENYL)-4-METHYL-5-THIAZOLECARBOXYLIC ACID
METABOLITE ACTIVE -> PARENT
URINE
Structure of 2-HYDROXYFEBUXOSTAT
METABOLITE ACTIVE -> PARENT
MAJOR
URINE
Structure of 2-(4-(2-CARBOXYPROPOXY)-3-CYANOPHENYL)-4-METHYL-5-THIAZOLECARBOXYLIC ACID
METABOLITE ACTIVE -> PARENT
MAJOR
FECAL
Structure of 2-HYDROXYFEBUXOSTAT
METABOLITE ACTIVE -> PARENT
It was reported that febuxostat is metabolized by oxidative and conjugation pathways and three major metabolites have been identified as 67M-1, 67M-2, and 67M-4
MAJOR
FECAL
Structure of 3-HYDROXYFEBUXOSTAT, (+/-)-
METABOLITE ACTIVE -> PARENT
It was reported that febuxostat is metabolized by oxidative and conjugation pathways and three major metabolites have been iden- tified as 67M-1, 67M-2, and 67M-4
MAJOR
FECAL
Structure of 3-HYDROXYFEBUXOSTAT, (+/-)-
METABOLITE ACTIVE -> PARENT
MAJOR
URINE
Related Record Type Details
Structure of FEBUXOSTAT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC HIGH-FAT MEAL

FED CONDITION

Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
NIH
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