FEBUXOSTAT MAGNESIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C16H15N2O3S.Mg
Molecular Weight	655.039
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Mg++].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=BNABHEFFEDHWIR-UHFFFAOYSA-L

InChI=1S/2C16H16N2O3S.Mg/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);/q;;+2/p-2

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.	2003 Dec	14735233
An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition.	2003 Jan 17	12421831
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	15190124
Gateways to clinical trials.	2004 Sep	15538546
Febuxostat--treatment for hyperuricemia and gout?	2005 Dec 8	16339099
Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment.	2005 Jan-Feb	15662289
Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout.	2005 Jul	16022578
Gateways to clinical trials.	2005 Jun	16082422
Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase.	2005 Mar 4	15698861
Pathophysiology, clinical presentation and treatment of gout.	2006	16956303
A concise history of gout and hyperuricemia and their treatment.	2006	16820040
Gateways to clinical trials.	2006 Apr	16810345
Febuxostat versus allopurinol for gout.	2006 Apr 6	16602151
Febuxostat versus allopurinol for gout.	2006 Apr 6	16598054
Febuxostat for prevention of gout attacks.	2006 Aug	16958189
Newer therapeutic approaches: gout.	2006 Feb	16504833
The effect of mild and moderate hepatic impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase.	2006 Jan	16397288
[Gout].	2006 Jan 11	16463802
Gateways to clinical trials.	2006 Jul-Aug	16894408
New developments in clinically relevant mechanisms and treatment of hyperuricemia.	2006 Jun	16901081
Is febuxostat a more effective treatment for hyperuricemia and gout than allopurinol?	2006 May	16932692
Case 8: initiation of urate-lowering therapy for standard advanced gout.	2006 Nov	17059910
Emerging therapies in the long-term management of hyperuricaemia and gout.	2007 Apr	17388867
Gateways to clinical trials.	2007 Dec	18200333
Tumor lysis syndrome.	2007 Jun	17525897
Developments in the scientific and clinical understanding of gout.	2008	18947374
Gateways to clinical trials.	2008 Apr	18597009
Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects.	2008 Mar	17953718
Gateways to clinical trials.	2008 Oct	19088949
Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?	2009	19725932
Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress.	2009	19436671
A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout.	2009 Apr	19296886
Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.	2009 Feb	19141576
Febuxostat (Uloric) for chronic treatment of gout.	2009 May 18	19448587
Approach to the treatment of hyperuricemia.	2009 Nov	19999894
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 MAGNESIUM

Common Name

English

5-THIAZOLECARBOXYLIC ACID, 2-(3-CYANO-4-(2-METHYLPROPOXY)PHENYL)-4-METHYL-, MAGNESIUM SALT (2:1)

Common Name

English

Code System Code Type Description

PUBCHEM

141336381

Created by admin on Sat Dec 16 14:31:28 GMT 2023 , Edited by admin on Sat Dec 16 14:31:28 GMT 2023

PRIMARY

CAS

1456533-39-3

Created by admin on Sat Dec 16 14:31:28 GMT 2023 , Edited by admin on Sat Dec 16 14:31:28 GMT 2023

PRIMARY

FDA UNII

4UB2J8Q7HG

Created by admin on Sat Dec 16 14:31:28 GMT 2023 , Edited by admin on Sat Dec 16 14:31:28 GMT 2023

PRIMARY

ACTIVE MOIETY


					101V0R1N2E

FEBUXOSTAT

SUBSTANCE RECORD


					4UB2J8Q7HG

FEBUXOSTAT MAGNESIUM

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