FEBUXOSTAT HEMIHYDRATE

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 Search

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

Description
Sources: http://www.drugbank.ca/drugs/DB04854
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

Targets

Primary Target	Pharmacology	Condition	Potency
Xanthine dehydrogenase 32 Target ID: CHEMBL1929 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24508129	Inhibitor 8297		1.26 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperuricemia in patients with gout 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_Lbl.pdf	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

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inducer 389 substrate 1037 inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other 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

Target	Modality	Activity	Clinical evidence
CYP1A 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=11 Page: 11.0	low
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=11 Page: 11.0	low
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=11 Page: 11.0	low
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=11 Page: 11.0	low
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=11 Page: 11.0	low
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021856s013lbl.pdf#page=13 Page: 38,13	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021856s013lbl.pdf#page=13 Page: 38,13
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#PAGE=38 Page: 38.0	no [Ki >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#PAGE=38 Page: 38.0	no [Ki >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#PAGE=38 Page: 38.0	no [Ki >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#PAGE=38 Page: 38.0	no [Ki >100 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	inconclusive
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=38 Page: 38.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=12 Page: 12,20,38	yes	no (co-administration study) Comment: warfarin: no effect at steady-state Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf#page=12 Page: 12,20,38

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Gateways to clinical trials.	2007 Dec	18200333
Febuxostat: a novel non-purine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in gout.	2007 Feb	19075968
Developments in the scientific and clinical understanding of gout.	2008	18947374
Febuxostat : a viewpoint by N. Lawrence Edwards.	2008	18729540
Febuxostat : a viewpoint by Naomi Schlesinger.	2008	18729539
Febuxostat: a viewpoint by H. Ralph Schumacher Jr and Lan X. Chen.	2008	18729538
Febuxostat.	2008	18729537
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?	2008	18636784
Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia.	2008	18434753
Gateways to clinical trials.	2008 Apr	18597009
[New antihyperuricemic medicine: febuxostat, Puricase, etc].	2008 Apr	18409528
[Inhibitors of xanthine oxidoreductase].	2008 Apr	18409526
Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome.	2008 Apr	18216151
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.	2008 Apr	18048425
Febuxostat in the management of hyperuricemia and chronic gout: a review.	2008 Dec	19337428
Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors: allopurinol, febuxostat, and FYX-051.	2008 Feb	18360072
Chronic xanthine oxidase inhibition following myocardial infarction in rabbits: effects of early versus delayed treatment.	2008 Feb 27	18215719
Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.	2008 Jun	18600509
Refractory gout: what is it and what to do about it?	2008 Mar	18349751
Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects.	2008 Mar	17953718
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	18421623
Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice.	2008 Nov	18995179
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	18975369
Gout management: let's get it right this time.	2008 Nov 15	18975368
Gateways to clinical trials.	2008 Oct	19088949
The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.	2008 Sep	18635756
The role of urate and xanthine oxidase in vascular oxidative stress: future directions.	2009	19851527
Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?	2009	19725932
Gout. Novel therapies for treatment of gout and hyperuricemia.	2009	19664185
Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress.	2009	19436671
Febuxostat: new drug. Hyperuricaemia: risk of gout attacks.	2009 Apr	19585722
Gateways to clinical trials.	2009 Apr	19536362
Febuxostat: a new agent for lowering serum urate.	2009 Apr	19499090
A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout.	2009 Apr	19296886
New gout treatment approved.	2009 Apr 1	19299362
Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates.	2009 Apr 16	19296639
Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.	2009 Feb	19141576
Gout Study Group: update on hyperuricemia and gout.	2009 Jul	19559637
Gout--what are the treatment options?	2009 Jun	19463070
Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.	2009 Jun	19286847
Update on emerging urate-lowering therapies.	2009 Mar	19339925
Febuxostat.	2009 Mar	19247302
Febuxostat: a new treatment for hyperuricaemia in gout.	2009 May	19447778
Febuxostat (Uloric) for chronic treatment of gout.	2009 May 18	19448587
New drugs: Febuxostat, lacosamide, and rufinamide.	2009 May-Jun	19443330
Approach to the treatment of hyperuricemia.	2009 Nov	19999894
[Crystal-induced activation of the inflammasome: gout and pseudogout].	2009 Nov	19838718
Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.	2009 Oct	19846027
Update on gout and hyperuricemia.	2010 Feb	19909378
Update on gout: new therapeutic strategies and options.	2010 Jan	20046204

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

In Vitro Use Guide

Febuxostat (200uM) inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages.

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

ACTIVE MOIETY


					101V0R1N2E

FEBUXOSTAT

SUBSTANCE RECORD


					7KC4X53ED3

FEBUXOSTAT HEMIHYDRATE

Details

SMILES

InChI

DescriptionSources: http://www.drugbank.ca/drugs/DB04854Curator's Comment: Description was created based on several sources, including https://www.drugs.com/uloric.html

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.drugbank.ca/drugs/DB04854
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/uloric.html

C_max

T_1/2

F_unbound

Drug as perpetrator