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-1 125 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 8228		149.0 µM [IC50]
Cyclooxygenase-2 192 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 8228		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 8360	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 9.5921281E11
Rheumatoid arthritis 313 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary		Approved 8360	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 9.5921281E11

C_max

Value	Dose	Analyte	Population
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
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
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

AUC

Value	Dose	Analyte	Population
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
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
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

T_1/2

Value	Dose	Analyte	Population
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
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
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

Doses

Dose	Population	Adverse events
2 g 1 times / day steady, oral (max) 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 Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	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 Page: 9

AEs

AE	Significance	Dose	Population
Dyspepsia	0.8% Disc. AE	2 g 1 times / day steady, oral (max) 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 Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9
Abdominal pain	1.1% Disc. AE	2 g 1 times / day steady, oral (max) 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 Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9
Diarrhea	1.3% Disc. AE	2 g 1 times / day steady, oral (max) 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 Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 660 CYP2C19 985 CYP2E1 648 CYP2A6 523 CYP2C8 688 CYP3A5 391 CYP1A1 348 alcohol dehydrogenase 6 ALDH 6 FMO1 16 FMO3 66 11-beta-HSD 3 AKR1C4 6 AKR1C1 19 AKR1C2 9

Drug as victim

Target	Modality	Activity	Metabolite
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	no
FMO1 16	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
FMO3 66	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
CYP2C8 688	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A5 391	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
11-beta-HSD 3	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C1 19	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C2 9	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C4 6	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
ALDH 6	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MN-CHO 1
CYP1A1 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2B6 660	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
alcohol dehydrogenase 6	substrate 3326 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
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
eMolecules	592792	https://www.emolecules.com/cgi-bin/more?vid=592792

PubMed

Title	Date	PubMed
Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.	2001	11701998
Cyclooxygenase selectivity of non-steroid anti-inflammatory drugs in humans: ex vivo evaluation.	2001 Aug 24	11525777
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
Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes.	2001 Dec	11804398
Comparison of the efficacy and safety of naproxen CR and nabumetone in the treatment of patients with osteoarthritis of the knee.	2001 Dec	11770835
Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.	2001 Dec	11736732
The ever-emerging anti-inflammatories. Have there been any real advances?	2001 Jan-Dec	11595413
The effects of nabumetone, a cyclooxygenase-2 inhibitor, on cisplatin-induced 5-hydroxytryptamine release from the isolated rat ileum.	2001 Jul-Aug	12090350
[Comparison of the efficacy and safety of nabumetone and diclofenac sodium in the treatment of patients with rheumatoid arthritis].	2001 May 10	11809123
[Evaluation of early biomarkers of cartilage degeneration in the diagnosis and clinico-therapeutic monitoring of primary osteoarthrosis].	2001 May-Jun	11692536
[Side effects cause enormous costs. Expensive arthritis therapy].	2001 Nov 15	11759607
Gastrointestinal medications and procedures in osteoarthritis patients treated with rofecoxib compared with nonselective NSAIDs.	2001 Nov 16	11965201
Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib.	2001 Nov 6	11696466
Nonsteroidal anti-inflammatory drugs for perioperative pain control.	2001 Oct	11693050
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
Dose-effect relationships of nonsteroidal anti-inflammatory drugs: a literature review.	2002 Aug	12240779
Drug-induced erythroderma with high fever.	2002 Feb	11890295
Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).	2002 Jan 15	11792343
Nonsteroidal antiinflammatory drug-induced pseudoporphyria: a case series.	2002 Jul-Aug	12118363
A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers.	2002 Jun	12047490
The different patterns of blood pressure elevation by rofecoxib and nabumetone.	2002 Jun	12037700
Medication toxicity among patients with ankylosing spondylitis.	2002 Jun 15	12115151
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
Structure-function relationship and role of tumor necrosis factor-alpha-converting enzyme in the down-regulation of L-selectin by non-steroidal anti-inflammatory drugs.	2002 Oct 11	12147693
COX-2: where are we in 2003?--distinction from NSAIDs becoming blurred.	2003	12723976
[Nabumetone is an alternative].	2003 Apr 24	12756699
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
Risk of breast cancer among users of aspirin and other anti-inflammatory drugs.	2004 Aug 2	15226764
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
General principles of pharmaceutical solid polymorphism: a supramolecular perspective.	2004 Feb 23	14962581
Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design.	2004 Nov	15339804
[Reflections on COX, Vioxx and Relifex. Increased cardiovascular risk following selective COX-2 inhibition].	2004 Nov 25	15631229
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Subjective impact of osteoarthritis flare-ups on patients' quality of life.	2005 Mar 16	15771777
Comparative effects of indomethacin and nabumetone on urine and electrolyte output in conscious rats.	2005 Nov	16293937
Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population.	2005 Nov 29	16316472
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
Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.	2006 Feb	16469680

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

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

RELAFEN

Brand 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