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

Molecular Formula	C15H16O2
Molecular Weight	228.2863
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis.	2001	11398914
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.	2001	11228592
[Laparoscopic splenectomy in pediatric hematologic diseases].	2001 Apr	11480196
A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis.	2001 Apr	11405384
Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines.	2001 Aug	11506967
Cyclooxygenase selectivity of non-steroid anti-inflammatory drugs in humans: ex vivo evaluation.	2001 Aug 24	11525777
Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.	2001 Dec	11736732
Management of nonsteroidal anti-inflammatory drug-related peptic ulcer bleeding.	2001 Jan 8	11165993
Association of immunological disorders in lethal side effect of NSAIDs on beta-glucan-administered mice.	2001 Jul	11476975
The effects of nabumetone, a cyclooxygenase-2 inhibitor, on cisplatin-induced 5-hydroxytryptamine release from the isolated rat ileum.	2001 Jul-Aug	12090350
Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.	2001 Jun	11459290
[Evaluation of early biomarkers of cartilage degeneration in the diagnosis and clinico-therapeutic monitoring of primary osteoarthrosis].	2001 May-Jun	11692536
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
A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers.	2002 Jun	12047490
In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon.	2002 Nov	12428657
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
Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors.	2003 Feb	12559680
Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies.	2003 Jun 1	12763542
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
Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin.	2004	15132714
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
General principles of pharmaceutical solid polymorphism: a supramolecular perspective.	2004 Feb 23	14962581
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
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
Pulp-dentine complex changes and root resorption during intrusive orthodontic tooth movement in patients prescribed nabumetone.	2005 Jan	15614010
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
Comparative effects of indomethacin and nabumetone on urine and electrolyte output in conscious rats.	2005 Nov	16293937
Picture of the month. Stevens-Johnson Syndrome.	2006 Aug	16894078

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.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:15:39 UTC 2023` Edited by `admin` on `Wed Jul 05 23:15:39 UTC 2023`
Record UNII	LW0TIW155Z
Record Status	`Validated (UNII)`
Record Version

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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