NABUMETONE

First approved in 1991

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H16O2
Molecular Weight	228.2869
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)CCc1ccc2cc(ccc2c1)OC

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:: 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-1 123 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 7701		149 µM [IC50]
Cyclooxygenase-2 188 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 7701	Osteoarthritis Rheumatoid arthritis	230 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoarthritis 152 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary	Cyclooxygenase-2	Approved 7997	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 959212800000
Rheumatoid arthritis 294 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary	Cyclooxygenase-2	Approved 7997	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 959212800000

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 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 1470	substrate 865	substrate 1038

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 575 CYP2C19 830 CYP2E1 567 CYP2A6 452 CYP2C8 586 CYP3A5 346 CYP1A1 302 alcohol dehydrogenase 6 ALDH 5 FMO1 13 FMO3 49 11-beta-HSD 3 AKR1C4 5 AKR1C1 18 AKR1C2 8

Drug as victim

Target	Modality	Activity	Metabolite
CYP2A6 452	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	no
FMO1 13	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
FMO3 49	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
CYP2C8 586	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP2C9 865	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A4 1470	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A5 346	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
11-beta-HSD 3	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C1 18	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C2 8	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C4 5	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
ALDH 5	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MN-CHO 1
CYP1A1 302	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2B6 575	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2C19 830	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2D6 1038	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2E1 567	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
alcohol dehydrogenase 6	substrate 2752 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
MolPort	MolPort-001-793-710	https://www.molport.com/shop/molecule-link/MolPort-001-793-710
ZINC	ZINC000000020221	http://zinc15.docking.org/substances/ZINC000000020221

PubMed

Title	Date	PubMed
Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes.	1999 May	10328874
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
Effect of nabumetone and aspirin on colonic mucosal bleeding time.	2001 Apr	11284783
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
Comparison of the efficacy and safety of naproxen CR and nabumetone in the treatment of patients with osteoarthritis of the knee.	2001 Dec	11770835
The ever-emerging anti-inflammatories. Have there been any real advances?	2001 Jan-Dec	11595413
Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.	2001 Jun	11459290
[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
2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.	2002 Apr 18	11960558
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
A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers.	2002 Jun	12047490
Medication toxicity among patients with ankylosing spondylitis.	2002 Jun 15	12115151
[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
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
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
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
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
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
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
Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.	2005 Aug	16124404
Rofecoxib for osteoarthritis.	2005 Jan 25	15654705
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
Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk.	2006	16808554
Tolerance of diclofenac after hypersensitivity to celecoxib and to nabumetone.	2006 Apr	16542210
Picture of the month. Stevens-Johnson Syndrome.	2006 Aug	16894078
Treatment of patients with osteoarthritis with rofecoxib compared with nabumetone.	2006 Feb	16484875
NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland.	2006 Jul	16731535
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

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]

Common Name

English

NABUMETONE [USP MONOGRAPH]

Common Name

English

NABUMETONE [MI]

Common Name

English

NABUMETONE [EP MONOGRAPH]

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

NABUMETONE [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

M01AX01