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Details

Stereochemistry ACHIRAL
Molecular Formula 2C16H16N2O3S.H2O
Molecular Weight 650.765
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEBUXOSTAT HEMIHYDRATE

SMILES

O.CC(C)COC1=C(C=C(C=C1)C2=NC(C)=C(S2)C(O)=O)C#N.CC(C)COC3=C(C=C(C=C3)C4=NC(C)=C(S4)C(O)=O)C#N

InChI

InChIKey=PBDGWWSMDHCTAJ-UHFFFAOYSA-N
InChI=1S/2C16H16N2O3S.H2O/c2*1-9(2)8-21-13-5-4-11(6-12(13)7-17)15-18-10(3)14(22-15)16(19)20;/h2*4-6,9H,8H2,1-3H3,(H,19,20);1H2

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
Molecular Formula H2O
Molecular Weight 18.0153
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
359
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 1.26 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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
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
1587
inducer
389

substrate
1037

inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2C19
1478
CYP1A2
1054

CYP2C8
693

CYP1A1
349

UGT1A1
418

UGT1A3
422

UGT1A9
380

UGT2B7
389

P-gp
1537
CYP1A
56

CYP2B6
547

CYP2C19
293

CYP3A4/5
124
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A
121
 low
CYP2B6
1001
 low
CYP2C19
1553
 low
CYP2C9
1819
 low
CYP3A4/5
335
 low
CYP2D6
1891
 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
1692
 no [Ki >100 uM]
CYP2C19
1553
 no [Ki >100 uM]
CYP2C9
1819
 no [Ki >100 uM]
CYP3A4
1925
 no [Ki >100 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 inconclusive
CYP1A1
349
 yes
CYP1A2
1054
 yes
CYP2C8
693
 yes
UGT1A1
418
 yes
UGT1A3
422
 yes
UGT1A9
380
 yes
UGT2B7
389
 yes
CYP2C9
1037
 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
Hyperuricemia and gout: new insights into pathogenesis and treatment.
2007
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
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
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?
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
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
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
Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?
2009
Gout. Novel therapies for treatment of gout and hyperuricemia.
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
Gateways to clinical trials.
2009 Apr
Febuxostat: a new agent for lowering serum urate.
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
Febuxostat: a new treatment for hyperuricaemia in gout.
2009 May
Febuxostat (Uloric) for chronic treatment of gout.
2009 May 18
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

Patents

20060252808
5
20080038242
3
20080096904
3
20080145846
3

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 Sat Dec 16 14:30:14 GMT 2023
Edited
by admin
on Sat Dec 16 14:30:14 GMT 2023
Record UNII
7KC4X53ED3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FEBUXOSTAT HEMIHYDRATE
Common Name English
2-(3-CYANO-4-ISOBUTYLOXYPHENYL)-4-METHYL-5-THIAZOLECARBOXYLIC ACID HEMIHYDRATE
Systematic Name English
FEBUXOSTAT HYDRATE
Common Name English
FEBUXOSTAT HYDRATE [JAN]
Common Name English
5-THIAZOLECARBOXYLIC ACID, 2-(3-CYANO-4-(2-METHYLPROPOXY)PHENYL)-4-METHYL-, HYDRATE (2:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
56963122
Created by admin on Sat Dec 16 14:30:14 GMT 2023 , Edited by admin on Sat Dec 16 14:30:14 GMT 2023
PRIMARY
FDA UNII
7KC4X53ED3
Created by admin on Sat Dec 16 14:30:14 GMT 2023 , Edited by admin on Sat Dec 16 14:30:14 GMT 2023
PRIMARY
CAS
442664-09-7
Created by admin on Sat Dec 16 14:30:14 GMT 2023 , Edited by admin on Sat Dec 16 14:30:14 GMT 2023
PRIMARY
SMS_ID
100000168509
Created by admin on Sat Dec 16 14:30:14 GMT 2023 , Edited by admin on Sat Dec 16 14:30:14 GMT 2023
PRIMARY
Related Record Type Details
Structure of FEBUXOSTAT
PARENT -> SALT/SOLVATE
Structure of FEBUXOSTAT
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of FEBUXOSTAT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
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