NABUMETONE

First approved in 1991

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H16O2
Molecular Weight	228.2863
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1)C=C(CCC(C)=O)C=C2

InChI

InChIKey=BLXXJMDCKKHMKV-UHFFFAOYSA-N

InChI=1S/C15H16O2/c1-11(16)3-4-12-5-6-14-10-15(17-2)8-7-13(14)9-12/h5-10H,3-4H2,1-2H3

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00461
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/nabumetone.html

Nabumetone is a naphthylalkanone. Is is a non-selective prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to prostaglandin G2 and prostaglandin G2 to prostaglandin H2. Prostaglandin H2 is the precursor to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. The parent compound is a prodrug that undergoes hepatic biotransformation to the active compound, 6-methoxy-2-naphthylacetic acid (6MNA). The analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a result of decreased prostaglandin synthesis. The parent compound is a prodrug, which undergoes hepatic biotransformation to the active component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of prostaglandin synthesis, most likely through binding to the COX-2 and COX-1 receptors. Nabumetone is used for acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis. Nabumetone has been developed by Beecham. It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 8504		149.0 µM [IC50]
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 8504		230.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoarthritis 157 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary		Approved 8583	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 2000
Rheumatoid arthritis 320 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary		Approved 8583	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 2000

C_max

Value	Dose	Analyte	Population
13.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN
21.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
52.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
66.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
204.98 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN
1120 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2150 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1022 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1270 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
16.82 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN
26.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
34.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g 1 times / day steady, oral Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf	Disc. AE: Diarrhea, Dyspepsia... AEs leading to discontinuation/dose reduction: Diarrhea (1.3%) Dyspepsia (0.8%) Abdominal pain (1.1%) Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf

AEs

AE	Significance	Dose	Population
Dyspepsia	0.8% Disc. AE	2 g 1 times / day steady, oral Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf
Abdominal pain	1.1% Disc. AE	2 g 1 times / day steady, oral Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf
Diarrhea	1.3% Disc. AE	2 g 1 times / day steady, oral Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 776 CYP2C19 1119 CYP2E1 729 CYP2A6 626 CYP2C8 810 CYP3A5 446 CYP1A1 389 alcohol dehydrogenase 7 ALDH 6 FMO1 25 FMO3 77 11-beta-HSD 3 AKR1C4 7 AKR1C1 22 AKR1C2 12

Drug as victim

Target	Modality	Activity	Metabolite
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	no
FMO1 25	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
FMO3 77	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
11-beta-HSD 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C2 12	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C4 7	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
ALDH 6	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MN-CHO 1
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
alcohol dehydrogenase 7	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MNE-ol 1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7443	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7443
ChemicalBook	CB2386779	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2386779
eMolecules	592792	https://www.emolecules.com/cgi-bin/more?vid=592792
MolPort	MolPort-001-793-710	https://www.molport.com/shop/molecule-link/MolPort-001-793-710
Selleck Chemicals	nabumetone	http://www.selleckchem.com/products/nabumetone.html
ZINC	ZINC000000020221	http://zinc15.docking.org/substances/ZINC000000020221

PubMed

Title	Date	PubMed
Use of nonsteroidal anti-inflammatory drugs and gastroprotective agents before the advent of cyclooxygenase-2-selective inhibitors: analysis of a large United States claims database.	2001 Dec	11813933
Gastrointestinal medications and procedures in osteoarthritis patients treated with rofecoxib compared with nonselective NSAIDs.	2001 Nov 16	11965201
A comparison of adverse renovascular experiences among osteoarthritis patients treated with rofecoxib and comparator non-selective non-steroidal anti-inflammatory agents.	2002	12017215
2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.	2002 Apr 18	11960558
Drug-induced erythroderma with high fever.	2002 Feb	11890295
Trends in medication use for osteoarthritis treatment.	2002 May	12022364
In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon.	2002 Nov	12428657
COX-2: where are we in 2003?--distinction from NSAIDs becoming blurred.	2003	12723976
Drug-induced erythroderma with high fever--is it drug hypersensitivity syndrome?	2003 Apr	12707474
An open label study to establish dosing recommendations for nabumetone in juvenile rheumatoid arthritis.	2003 Apr	12672207
[Nabumetone is an alternative].	2003 Apr 24	12756699
Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro.	2003 Aug	12730611
Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high-performance liquid chromatography with ultraviolet, fluorescence and mass spectrometric detection.	2003 Aug 8	12899954
Non-steroidal anti-inflammatory drug, nabumetone, prevents indometacin-induced gastric damage via inhibition of neutrophil functions.	2003 Feb	12635655
Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors.	2003 Feb	12559680
Determination of nabumetone in pharmaceutical formulation by flow injection analysis (FIA) with UV-detection.	2003 Jan	12622247
Safe full-dose one-step nabumetone challenge in patients with nonsteroidal anti-inflammatory drug hypersensitivity.	2003 Jul-Aug	12974196
Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies.	2003 Jun 1	12763542
Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study.	2003 Jun 2	12771981
Development of apoptosis-resistant dihydrofolate reductase-deficient Chinese hamster ovary cell line.	2003 Jun 30	12701155
[Meta-analysis on the effect and adverse reaction on patients with osteoarthritis and rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs].	2003 Nov	14687510
Selective COX-2 inhibition and cardiovascular effects: a review of the rofecoxib development program.	2003 Oct	14564311
Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis.	2004	15456329
Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin.	2004	15132714
Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.	2004 Dec	15700167
In vitro investigation of the effects of nonsteroidal anti-inflammatory drugs, prostaglandin E2, and prostaglandin F2alpha on contractile activity of the third compartment of the stomach of llamas.	2004 Feb	14974580
Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal anti-inflammatory drugs in a cohort of coumarin users: a pharmacoeconomic analysis linked to a case-control study.	2004 Jul	15336481
Adverse effect of drug-induced emotional problems on work and daily activities. A principal component as an independent predictor of ADRs in Shanghai patients with osteo-arthropathy taking nabumetone.	2004 Jun	15222724
Risk factors of adverse drug reaction from non-steroidal anti-inflammatory drugs in Shanghai patients with arthropathy.	2004 Mar	15000891
Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectrometric detection.	2004 Mar 26	15058587
Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.	2004 Mar-Apr	15161036
A population based historical cohort study of the mortality associated with nabumetone, Arthrotec, diclofenac, and naproxen.	2004 May	15124256
Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial.	2004 May	15086644
Pain management in osteoarthritis: a focus on onset of efficacy--a comparison of rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials.	2004 Nov	15556830
Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design.	2004 Nov	15339804
Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory drugs associated with exacerbations of inflammatory bowel disease?	2004 Nov 15	15569105
[Reflections on COX, Vioxx and Relifex. Increased cardiovascular risk following selective COX-2 inhibition].	2004 Nov 25	15631229
The upper gastrointestinal safety of rofecoxib vs. NSAIDs: an updated combined analysis.	2004 Oct	15462687
Effect of the addition of water-soluble polymers on the interfacial properties of aerosol OT vesicles.	2004 Oct 15	15450468
Patient characteristics associated with outpatient prescriptions for nabumetone and oxaprozin versus celecoxib and rofecoxib.	2005 Apr 1	15790802
Simplex optimization of the variables affecting the micelle-stabilized room temperature phosphorescence of 6-methoxy-2-naphthylacetic acid and its kinetic determination in human urine.	2005 Apr 1	15766723
Pulp-dentine complex changes and root resorption during intrusive orthodontic tooth movement in patients prescribed nabumetone.	2005 Jan	15614010
The nonsteroidal anti-inflammatory drug, nabumetone, differentially inhibits beta-catenin signaling in the MIN mouse and azoxymethane-treated rat models of colon carcinogenesis.	2005 Jan 20	15617833
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Development and validation of a reversed-phase liquid chromatographic method for separation and simultaneous determination of COX-2 inhibitors in pharmaceuticals and its application to biological fluids.	2005 Jun	15627281
Subjective impact of osteoarthritis flare-ups on patients' quality of life.	2005 Mar 16	15771777
Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk.	2006	16808554
Picture of the month. Stevens-Johnson Syndrome.	2006 Aug	16894078
Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.	2006 Jun	16786056
Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics and solubility: a technical note.	2006 May 26	16796365

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: 1000 mg orally once a day Maintenance dose: 1500 to 2000 mg orally per day in 1 or 2 divided doses Maximum dose: 2000 mg/day

Route of Administration: Oral

In Vitro Use Guide

Nabumetone (50 ug/ml) was found to significantly increase COX-2 at mRNA levels but directly suppress the concentration of PGE2 in culture medium of human intervertebral disc cells.

Name

Type

Language

RELAFEN

Preferred Name

English

NABUMETONE

Official Name

English

NABUMETONE [VANDF]

Common Name

English

NABUMETONE [USP-RS]

Common Name

English

BRL-14777

Code

English

NABUMETONE [ORANGE BOOK]

Common Name

English

NABUMETONE [JAN]

Common Name

English

NABUMETONE [MART.]

Common Name

English

2-BUTANONE, 4-(6-METHOXY-2-NAPHTHALENYL)-

Systematic Name

English

NABUMETONE [USP MONOGRAPH]

Common Name

English

Nabumetone [WHO-DD]

Common Name

English

NABUMETONE [MI]

Common Name

English

NABUMETONE [EP MONOGRAPH]

Common Name

English

NABUMETONE [USP IMPURITY]

Common Name

English

nabumetone [INN]

Common Name

English

4-(6-Methoxy-2-naphthyl)-2-butanone

Systematic Name

English

NABUMETONE [USAN]

Common Name

English

NSC-758623

Code

English

Classification Tree Code System Code

WHO-ATC

M01AX01