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Details

Stereochemistry ACHIRAL
Molecular Formula C16H16N2O3S
Molecular Weight 316.375
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEBUXOSTAT

SMILES

CC(C)COC1=C(C=C(C=C1)C2=NC(C)=C(S2)C(O)=O)C#N

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 316.375
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.26 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Uloric

Approved Use

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

Launch Date

2009
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.53 μg/mL
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
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
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%
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:
healthy, adult
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:
unhealthy, adult
n = 757
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 757
Sources:
Disc. AE: Function liver abnormal...
AEs leading to
discontinuation/dose reduction:
Function liver abnormal (1.8%)
Sources:
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:
unhealthy, adult
n = 1279
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 1279
Sources:
Disc. AE: Function liver abnormal...
AEs leading to
discontinuation/dose reduction:
Function liver abnormal (1.2%)
Sources:
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:
unhealthy, adult
n = 757
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 757
Sources:
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:
unhealthy, adult
n = 1279
Health Status: unhealthy
Condition: hyperuricemia | gout
Age Group: adult
Sex: M+F
Population Size: 1279
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
low
low
low
low
low
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
no [Ki >100 uM]
no [Ki >100 uM]
no [Ki >100 uM]
no [Ki >100 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
inconclusive
yes
yes
yes
yes
yes
yes
yes
yes
no (co-administration study)
Comment: warfarin: no effect at steady-state
Page: 12,20,38
PubMed

PubMed

TitleDatePubMed
Gateways to clinical trials.
2003 Dec
An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition.
2003 Jan 17
Gateways to clinical trials.
2003 Jan-Feb
Y-700 [1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid]: a potent xanthine oxidoreductase inhibitor with hepatic excretion.
2004 Nov
Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia.
2004 Oct
PK/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild and moderate renal impairment.
2004 Oct
Febuxostat--treatment for hyperuricemia and gout?
2005 Dec 8
Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout.
2005 Mar
Febuxostat (Teijin/Ipsen/TAP).
2005 Nov
Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs.
2006 Aug
Newer therapeutic approaches: gout.
2006 Feb
Acute effects of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in pacing induced heart failure.
2006 Nov
Case 8: initiation of urate-lowering therapy for standard advanced gout.
2006 Nov
[Febuxostat versus allopurinol for hyperuricemia].
2006 Oct
Hyperuricemia and gout: new insights into pathogenesis and treatment.
2007
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
Developments in the scientific and clinical understanding of gout.
2008
Febuxostat : a viewpoint by Naomi Schlesinger.
2008
Febuxostat: a viewpoint by H. Ralph Schumacher Jr and Lan X. Chen.
2008
Febuxostat.
2008
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?
2008
[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
Chronic xanthine oxidase inhibition following myocardial infarction in rabbits: effects of early versus delayed treatment.
2008 Feb 27
Refractory gout: what is it and what to do about it?
2008 Mar
Gout management: let's get it right this time.
2008 Nov 15
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
New gout treatment approved.
2009 Apr 1
Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates.
2009 Apr 16
Gout Study Group: update on hyperuricemia and gout.
2009 Jul
Gout--what are the treatment options?
2009 Jun
New drugs: Febuxostat, lacosamide, and rufinamide.
2009 May-Jun
Approach to the treatment of hyperuricemia.
2009 Nov
[Crystal-induced activation of the inflammasome: gout and pseudogout].
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

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
Febuxostat (200uM) inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:50:40 GMT 2023
Edited
by admin
on Fri Dec 15 15:50:40 GMT 2023
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 [WHO-DD]
Common 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
ULORIC
Brand Name English
FEBUXOSTAT [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548645
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
WHO-VATC QM04AA03
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
EMA ASSESSMENT REPORTS ADENURIC (AUTHORIZED: GOUT)
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
WHO-ATC M04AA03
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
NDF-RT N0000175698
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
NDF-RT N0000000206
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
NCI_THESAURUS C1637
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
NCI_THESAURUS C921
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
Code System Code Type Description
FDA UNII
101V0R1N2E
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
WIKIPEDIA
Febuxostat
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
DRUG BANK
DB04854
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
NCI_THESAURUS
C65629
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
USAN
OO-12
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
MESH
C084623
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
EVMPD
SUB25382
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
DRUG CENTRAL
1137
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
INN
8140
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
CHEBI
31596
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
EPA CompTox
DTXSID8048650
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
DAILYMED
101V0R1N2E
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
RXCUI
73689
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY RxNorm
SMS_ID
100000089380
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
MERCK INDEX
m5253
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1164729
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
IUPHAR
6817
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
CAS
144060-53-7
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
PUBCHEM
134018
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
NSC
758874
Created by admin on Fri Dec 15 15:50:40 GMT 2023 , Edited by admin on Fri Dec 15 15:50:40 GMT 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
SOLVATE->ANHYDROUS
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
Related Record Type Details
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
METABOLITE ACTIVE -> PARENT
URINE
METABOLITE ACTIVE -> PARENT
MAJOR
URINE
METABOLITE ACTIVE -> PARENT
MAJOR
FECAL
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
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
METABOLITE ACTIVE -> PARENT
MAJOR
URINE
Related Record Type Details
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