Nabumetone

Identification

Summary

Nabumetone is an NSAID used to treat osteoarthritis and rheumatoid arthritis.

Brand Names

Relafen

Generic Name

Nabumetone

DrugBank Accession Number

DB00461

Background

Nabumetone was originally developed as a non-acidic non-steroidal anti-inflammatory drug (NSAID).^Label It was thought to avoid trapping of the drug in the stomach by making it unable to dissociate into ions which was believed to reduce GI toxicity by limiting local action.⁸ While slightly reduced, possibly due to a degree of cyclooxygenase-2 selectivity (COX-2), nabumetone still produces significant adverse effects in the GI tract.^Label,1 The molecule itself is a pro-drug with its 6-methoxy-2-naphthylacetic acid (6-MNA) metabolite acting as a potent COX inhibitor similar in structure to naproxen. Nabumetone was developed by Smithkline Beecham under the trade name Relafen and first received FDA approval in December, 1991.¹²

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 228.2863
Monoisotopic: 228.115029756
Chemical Formula: C₁₅H₁₆O₂

Synonyms

4-(6-Methoxy-2-naphthalenyl)-2-butanone
4-(6-Methoxy-2-naphthyl)-2-butanone
Nabumeton
Nabumetona
Nabumétone
Nabumetone
Nabumetonum

External IDs

BRL 14777
BRL-14777

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Pharmacology

Indication

Indicated for:^Label

1) Symptomatic relief in rheumatoid arthritis.

2) Symptomatic relief in osteoarthritis.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Symptomatic treatment of	Osteoarthritis		••••••••••••
Symptomatic treatment of	Rheumatoid arthritis		••••••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia.^9,6 This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited.

The anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells.^9,7 These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions.

The anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus.⁹ Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well.

The adverse effects of NSAIDs are related to their therapeutic effects.⁹ The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO₃^- secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of thrombosis.

Mechanism of action

Nabumetone's active metabolite, 6-MNA, is an inhibitor of both COX-1 and COX-2 although it exhibits some COX-2 selectivity.^Label,1 Inhibition of COX-1 and COX-2 reduces conversion of arachidonic acid to PGs and thromboxane (TXA₂). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone.

PGE₂ is the primary PG involved in modulation of nociception.⁶ It mediates peripheral sensitization through a variety of effects.^9,6 PGE₂ activates the G_q-coupled EP₁ receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE₂ also activates the EP₄ receptor, coupled to G_s, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE₂ act via EP₃ to increase sensitivity to bradykinin and via EP₂ to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP₂ receptor which couples to G_s. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI₂ is known to play a role via its G_s-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.

PGI₂ and PGE₂ contribute to acute inflammation via their IP and EP₂ receptors.^9,7 Similarly to β adrenergic receptors these are G_s-coupled and mediate vasodilation through the AC/PKA pathway. PGE₂ also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.⁹ PGD₂ plays a role in the activation of endothelial cell release of cytokines through its DP₁ receptor.⁷ PGI₂ and PGE₂ modulate T-helper cell activation and differentiation through IP, EP₂, and EP₄ receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.

PGE₂ can cross the blood-brain barrier and act on excitatory G_q EP₃ receptors on thermoregulatory neurons in the hypothalamus.⁹ This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE₂ thereby reducing the activity of these neurons.

The adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized.⁹ PGI₂ and PGE₂ regulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGE₂ also regulates gastric protection via EP₃ receptors which are, in this location, coupled to G_i which inhibits the AC/PKA pathway. This reduces the secretion of protons by H⁺/K⁺ ATPase in parietal cells and increases the secretion of mucus and HCO₃^- by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI₂, which opposes platelet aggregation, generation by COX-2 selective agents leads to an imbalance with TXA₂ generated by COX-1, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX-2 selective it is thought to promote this imbalance and increase thrombotic risk.¹

Target	Actions	Organism
AProstaglandin G/H synthase 2	inhibitor	Humans
UProstaglandin G/H synthase 1	inhibitor	Humans

Absorption

Nabumetone is well-absorbed from the GI tract and undergoes significant first pass metabolism resulting in approximately 35% being converted to the active metabolite, 6-MNA.^Label,1 Tmax for 6-MNA varies widely with a mean values of 3 and 11 hours reported in official product monographs, and described as 9-12 hours in published literature ^Label,10,1 Administration with food increases Cmax by 33% and increases absorption rate.^Label,1 If formulated as a suspension the Cmax increases and the Tmax is reduced by 0.8 hours while the all other pharmacokinetic parameters remain unchanged.¹

Volume of distribution

The Vd of 6-MNA reported after administration of a single dose is 0.1-0.2 L/kg or approximately 5-10 L.¹ Vdss reported in official product labeling is approximately 53 L.^Label,10

Protein binding

6-MNA is over 99% bound to plasma proteins, likely albumin.^Label,1 The unbound fraction is 0.1-0.2% and remains proportional in the dose range of 1000-2000mg

Metabolism

Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenase^2,3. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite.^4,3 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA).^2,3 Both 6-MNA and 6-HNA are further converted to conjugates.³ Other metabolites are generated through a mix of ketone reduction and O-demethylation along with subsequent conjugation. Glucuronide conjugates of several metabolites have been found to become further conjugated to glycine residues.⁵

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Nabumetone

Route of elimination

Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma.^Label,1 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation.

Half-life

6-MNA has a mean half-life of 24 hours with a range of 19-36 hours.^Label

Clearance

6-MNA has an apparent steady-state clearance of 20 - 30 mL/min.^Label

Adverse Effects

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Toxicity

LD₅₀ Values

Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP)¹¹

Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC)¹¹

Monkey: 3200 mg/kg (Oral)¹¹

Overdose

Signs and symptoms of nabumetone overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.^Label These are considered reversible with supportive care. GI bleeding, hypertension, acute kidney injury, respiratory depression, and coma are rare but can occur. No antidote exists for nabumetone overdose although administration of activated charcoal and/or induction of emesis can reduce absorption if the nabumetone dose was taken less than 4 hours prior.^Label,10 6-MNA is cannot be cleared by dialysis.

Carcinogenicity & Mutagenicity

Nabumetone was not significantly carcinogenic in rats or mice studied over 2 years.^Label Neither the Ames test nor mouse micronucleus test showed nabumetone or it's active metabolite, 6-MNA, to be mutagenic. Chromosomal abberation has been observed in cultured lymphocytes exposed to concentrations of 80 mcg/mL and higher of nabumetone or 6-MNA equivalent to the maximum recommended human dose.

Reproductive Toxicity

No adverse effects on fertility have been observed in male and female rats at doses of 320 mg/kg/day.^Label,10] No teratogenicity has been observed in pregnant rabbits or rats. Dystocia and delayed parturition have been noted in rats resulting in reduced survival of offspring. This has been attributed to the role of prostaglandins in uterine contraction. NSAIDs can also cause premature closure of the ductus ateriosus.

Lactation

6-MNA has been detected in the milk of lactating rats.^Label,10 While no data is available in humans, 6-MNA is both highly protein bound and exists in its anionic form in circulation. For these reasons partitioning into breast milk is expected to be limited.

Pathways

Pathway	Category
Nabumetone Action Pathway	Drug action

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Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Nabumetone may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abametapir	The serum concentration of Nabumetone can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Nabumetone can be increased when combined with Abatacept.
Abciximab	The risk or severity of bleeding and hemorrhage can be increased when Nabumetone is combined with Abciximab.
Abiraterone	The serum concentration of Nabumetone can be increased when it is combined with Abiraterone.

Food Interactions

Avoid alcohol. Alcohol use may aggravate the gastrointestinal irritation caused by this drug.
Take with food. Food increases the rate of absorption.

Products

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Product Images

International/Other Brands

Arthaxan (SmithKline Beecham (Germany; discontinued)) / Balmox (Beecham (Portugal), Meda (Switzerland)) / Dolsinal (Ferrer (Spain; discontinued)) / Listran (Uriach (Spain)) / Mebutan (Meda (Netherlands)) / Nabuser (Geymonat (Italy)) / Relif (Meda (Spain)) / Relifen (Sanwa (Japan), GSK (South Africa)) / Relifex (Meda (Czeck Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Italy, Norway, Sweden, United Kingdom), GSK (Israel, Mexico, Poland, Thailand, Turkey), SmithKline Beecham (Philippines))

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Nabumetone	Tablet	500 mg	Oral	Sanis Health Inc	2010-02-16	2017-02-08
Nabumetone	Tablet	500 mg	Oral	Apotex Corporation	Not applicable	Not applicable
Nabumetone	Tablet	500 mg	Oral	Aa Pharma Inc	1998-08-21	Not applicable
Nabumetone-500	Tablet	500 mg	Oral	Pro Doc Limitee	2008-04-07	2010-07-13
Relafen	Tablet, film coated	500 mg/1	Oral	Physicians Total Care, Inc.	1993-05-12	2011-05-31

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Mylan-nabumetone	Tablet	500 mg	Oral	Mylan Pharmaceuticals	2002-02-20	2017-01-09
Nabumetone	Tablet	500 mg/1	Oral	REMEDYREPACK INC.	2017-08-18	2020-05-01
Nabumetone	Tablet, film coated	500 mg/1	Oral	Carilion Materials Management	2011-06-13	Not applicable
Nabumetone	Tablet	750 mg/1	Oral	Northwind Pharmaceuticals	2021-07-07	Not applicable
Nabumetone	Tablet, film coated	750 mg/1	Oral	Quality Care Products, LLC	2019-06-14	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
NuDroxiPAK N-500	Nabumetone (500 mg/1) + Capsaicin (0.25 mg/1mL) + Menthol (60 mg/1mL) + Methyl salicylate (250 mg/1mL)	Kit	Oral; Topical	Nucare Pharmaceuticals,inc.	2018-03-16	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Relafen	Nabumetone (500 mg/1)	Tablet, film coated	Oral	Physicians Total Care, Inc.	1993-05-12	2011-05-31

Chemical Identifiers

UNII: LW0TIW155Z
CAS number: 42924-53-8
InChI Key: BLXXJMDCKKHMKV-UHFFFAOYSA-N
InChI: 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
IUPAC Name: 4-(6-methoxynaphthalen-2-yl)butan-2-one
SMILES: COC1=CC2=C(C=C1)C=C(CCC(C)=O)C=C2

References

Synthesis Reference

Brian F. Becnel, Mahmood Sabahi, Kevin J. Theriot, "Production of nabumetone or precursors thereof." U.S. Patent US5907069, issued December, 1985.

US5907069

General References

Davies NM: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clin Pharmacokinet. 1997 Dec;33(6):404-16. doi: 10.2165/00003088-199733060-00001. [Article]
Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [Article]
Nobilis M, Mikusek J, Szotakova B, Jirasko R, Holcapek M, Chamseddin C, Jira T, Kucera R, Kunes J, Pour M: Analytical power of LLE-HPLC-PDA-MS/MS in drug metabolism studies: identification of new nabumetone metabolites. J Pharm Biomed Anal. 2013 Jun;80:164-72. doi: 10.1016/j.jpba.2013.03.006. Epub 2013 Mar 19. [Article]
Turpeinen M, Hofmann U, Klein K, Murdter T, Schwab M, Zanger UM: A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes. Drug Metab Dispos. 2009 May;37(5):1017-24. doi: 10.1124/dmd.108.025700. Epub 2009 Feb 9. [Article]
Ceslova L, Holcapek M, Nobilis M: Identification of combined conjugation of nabumetone phase I metabolites with glucuronic acid and glycine in minipig biotransformation using coupling high-performance liquid chromatography with electrospray ionization mass spectrometry. J Pharm Biomed Anal. 2014 Jan;88:221-4. doi: 10.1016/j.jpba.2013.08.053. Epub 2013 Sep 12. [Article]
Chen L, Yang G, Grosser T: Prostanoids and inflammatory pain. Prostaglandins Other Lipid Mediat. 2013 Jul-Aug;104-105:58-66. doi: 10.1016/j.prostaglandins.2012.08.006. Epub 2012 Sep 3. [Article]
Hirata T, Narumiya S: Prostanoids as regulators of innate and adaptive immunity. Adv Immunol. 2012;116:143-74. doi: 10.1016/B978-0-12-394300-2.00005-3. [Article]
Blower PR: The unique pharmacologic profile of nabumetone. J Rheumatol Suppl. 1992 Nov;36:13-9. [Article]
Emer M. Smyth; Tilo Grosser; Garret A. FitzGerald (2018). 37 & 38. In Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
Nabumetone Health Canada Monograph [Link]
ChemIDplus: Nabumetone [Link]
FDA: Relafen [Link]
FDA Approved Products: Relafen (nabumetone) tablets [Link]

External Links

Human Metabolome Database: HMDB0014604
KEGG Drug: D00425
PubChem Compound: 4409
PubChem Substance: 46507729
ChemSpider: 4256
BindingDB: 40128
RxNav: 31448
ChEBI: 7443
ChEMBL: CHEMBL1070
ZINC: ZINC000000020221
Therapeutic Targets Database: DAP000735
PharmGKB: PA450572
PDBe Ligand: NBO
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Nabumetone

PDB Entries

3taj / 6ci6

FDA label

Download (243 KB)

MSDS

Download (29.8 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Osteoarthritis of the Knee	1
1	Completed	Not Available	Healthy Subjects (HS)	1
1	Completed	Other	Healthy Subjects (HS)	1
1	Completed	Treatment	Healthy Subjects (HS)	2
Not Available	Completed	Treatment	Osteoarthritis of the Knee	1

Pharmacoeconomics

Manufacturers

Actavis elizabeth llc
Copley pharmaceutical inc
Dr reddys laboratories ltd
Invagen pharmaceuticals inc
Matrix laboratories ltd
Par pharmaceutical
Sandoz inc
Teva pharmaceuticals usa inc
Smithkline beecham corp dba glaxosmithkline

Packagers

Altura Pharmaceuticals Inc.
Amerisource Health Services Corp.
Apotheca Inc.
A-S Medication Solutions LLC
Blenheim Pharmacal
Bryant Ranch Prepack
Cardinal Health
Caremark LLC
Corepharma LLC
Direct Dispensing Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Doctor Reddys Laboratories Ltd.
Eon Labs
Glenmark Generics Ltd.
H.J. Harkins Co. Inc.
Heartland Repack Services LLC
Innoviant Pharmacy Inc.
InvaGen Pharmaceuticals Inc.
Kaiser Foundation Hospital
Keltman Pharmaceuticals Inc.
Lake Erie Medical and Surgical Supply
Major Pharmaceuticals
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Novopharm Ltd.
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
Par Pharmaceuticals
PD-Rx Pharmaceuticals Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prescription Dispensing Service Inc.
Quality Care
Rebel Distributors Corp.
Redpharm Drug
Sandoz
Southwood Pharmaceuticals
St Mary's Medical Park Pharmacy
Stat Rx Usa
Teva Pharmaceutical Industries Ltd.
UDL Laboratories
Vangard Labs Inc.

Dosage Forms

Form	Route	Strength
Tablet	Oral	1 g
Tablet	Oral
Granule, for suspension	Oral	1 g
Suspension	Oral	1 g/10ml
Tablet, chewable	Oral	1 g
Tablet	Oral	1.0 G
Tablet, film coated	Oral
Tablet, coated	Oral	0.5 g
Tablet	Oral	500 mg/1
Tablet	Oral	750 mg/1
Tablet, film coated	Oral	500 1/1
Tablet, film coated	Oral	750 mg/1
Tablet, film coated	Oral	750 1/1
Tablet, film coated	Oral	1000 mg/1
Tablet	Oral	500 MG
Tablet, coated	Oral	1 G
Kit	Oral; Topical
Tablet	Oral	500 mg / tab
Tablet	Oral	750 mg / tab
Tablet, film coated	Oral	500 mg/1
Tablet	Oral	1000 mg/1
Tablet	Oral	750 mg
Granule, for suspension	Oral
Solution	Oral
Tablet, chewable	Oral
Tablet	Oral	1000 mg
Tablet, coated	Oral	500 mg
Tablet, film coated	Oral	500 mg

Prices

Unit description	Cost	Unit
Relafen 750 mg tablet	2.91USD	tablet
Relafen 500 mg tablet	2.82USD	tablet
Nabumetone 750 mg tablet	1.56USD	tablet
Nabumetone 500 mg tablet	1.32USD	tablet
Apo-Nabumetone 500 mg Tablet	0.39USD	tablet
Mylan-Nabumetone 500 mg Tablet	0.39USD	tablet
Novo-Nabumetone 500 mg Tablet	0.39USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	78-82	Health Canada Product Monograph, AA Pharma Inc.
water solubility	Practically insoluble	FDA Label, Eon Labs Inc.
logP	2400	FDA Label, Eon Labs Inc.

Predicted Properties

Property	Value	Source
Water Solubility	0.00193 mg/mL	ALOGPS
logP	3.41	ALOGPS
logP	3.22	Chemaxon
logS	-5.1	ALOGPS
pKa (Strongest Acidic)	19.59	Chemaxon
pKa (Strongest Basic)	-4.8	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	2	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	26.3 Å²	Chemaxon
Rotatable Bond Count	4	Chemaxon
Refractivity	68.43 m³·mol^-1	Chemaxon
Polarizability	26.17 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9401
Caco-2 permeable	+	0.9049
P-glycoprotein substrate	Substrate	0.5
P-glycoprotein inhibitor I	Non-inhibitor	0.5653
P-glycoprotein inhibitor II	Inhibitor	0.5656
Renal organic cation transporter	Non-inhibitor	0.7143
CYP450 2C9 substrate	Non-substrate	0.7664
CYP450 2D6 substrate	Non-substrate	0.7329
CYP450 3A4 substrate	Substrate	0.614
CYP450 1A2 substrate	Inhibitor	0.959
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.8591
CYP450 3A4 inhibitor	Non-inhibitor	0.8235
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6443
Ames test	Non AMES toxic	0.8942
Carcinogenicity	Non-carcinogens	0.8745
Biodegradation	Not ready biodegradable	0.8489
Rat acute toxicity	1.7384 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7536
hERG inhibition (predictor II)	Non-inhibitor	0.8059

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0006-7930000000-53550e3b73002ac9c671
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-00di-0900000000-af6f3d0d1c5f77f47279
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-00di-0900000000-6b7de93b51a79132630f
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-004i-4910000000-a4f59053ed0ee04bb88f
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00di-0900000000-6b7de93b51a79132630f
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00di-0900000000-af6f3d0d1c5f77f47279
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00fr-2900000000-53d7d6dc809a154d16c2
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-004i-0190000000-ec5d9bb172002e0e4927
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0udi-1900000000-b859143f455f13b8a17b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-0690000000-406dd127389b78c59a4d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0pdi-1940000000-bf4db589b374b919749f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-05ic-2900000000-eb834198b48ae4a007b3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00kf-1900000000-19a7c1fbf1ac265d7ec5
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	166.4135864	predicted	DarkChem Lite v0.1.0
[M-H]-	166.5326864	predicted	DarkChem Lite v0.1.0
[M-H]-	156.72418	predicted	DeepCCS 1.0 (2019)
[M+H]+	167.5110864	predicted	DarkChem Lite v0.1.0
[M+H]+	167.6450864	predicted	DarkChem Lite v0.1.0
[M+H]+	159.08217	predicted	DeepCCS 1.0 (2019)
[M+Na]+	166.3463864	predicted	DarkChem Lite v0.1.0
[M+Na]+	166.6696864	predicted	DarkChem Lite v0.1.0
[M+Na]+	165.17532	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	>10000	N/A	N/A	A5629 / A27471

Details1. Prostaglandin G/H synthase 2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Prostaglandin-endoperoxide synthase activity
Specific Function: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name: PTGS2
Uniprot ID: P35354
Uniprot Name: Prostaglandin G/H synthase 2
Molecular Weight: 68995.625 Da

References

Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics--theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. [Article]
Roy HK, Karolski WJ, Ratashak A: Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone. Int J Cancer. 2001 May 15;92(4):609-15. [Article]
van Kraaij DJ, Hovestad-Witterland AH, de Metz M, Vollaard EJ: A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers. Br J Clin Pharmacol. 2002 Jun;53(6):644-7. [Article]
Hedner T, Samulesson O, Wahrborg P, Wadenvik H, Ung KA, Ekbom A: Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. Drugs. 2004;64(20):2315-43; discussion 2344-5. [Article]
Elliott SN, McKnight W, Cirino G, Wallace JL: A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology. 1995 Aug;109(2):524-30. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Details2. Prostaglandin G/H synthase 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Prostaglandin-endoperoxide synthase activity
Specific Function: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name: PTGS1
Uniprot ID: P23219
Uniprot Name: Prostaglandin G/H synthase 1
Molecular Weight: 68685.82 Da

References

Giuliano F, Ferraz JG, Pereira R, de Nucci G, Warner TD: Cyclooxygenase selectivity of non-steroid anti-inflammatory drugs in humans: ex vivo evaluation. Eur J Pharmacol. 2001 Aug 24;426(1-2):95-103. [Article]
Takeuchi K, Smale S, Premchand P, Maiden L, Sherwood R, Thjodleifsson B, Bjornsson E, Bjarnason I: Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202. [Article]
Cipollone F, Ganci A, Panara MR, Greco A, Cuccurullo F, Patrono C, Patrignani P: Effects of nabumetone on prostanoid biosynthesis in humans. Clin Pharmacol Ther. 1995 Sep;58(3):335-41. [Article]
Bensen W, Zizzo A: Newer, safer nonsteroidal anti-inflammatory drugs. Rational NSAID selection for arthritis. Can Fam Physician. 1998 Jan;44:101-2, 105-7. [Article]

Enzymes

Details1. Myeloperoxidase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Peroxidase activity
Specific Function: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name: MPO
Uniprot ID: P05164
Uniprot Name: Myeloperoxidase
Molecular Weight: 83867.71 Da

References

Saleh TS, Calixto JB, Medeiros YS: Effects of anti-inflammatory drugs upon nitrate and myeloperoxidase levels in the mouse pleurisy induced by carrageenan. Peptides. 1999;20(8):949-56. [Article]

Details2. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Curator comments: Data supporting this enzyme action are limited to one in vitro study.

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58293.76 Da

References

Turpeinen M, Hofmann U, Klein K, Murdter T, Schwab M, Zanger UM: A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes. Drug Metab Dispos. 2009 May;37(5):1017-24. doi: 10.1124/dmd.108.025700. Epub 2009 Feb 9. [Article]

Details3. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Matsumoto K, Nemoto E, Hasegawa T, Akimoto M, Sugibayashi K: In vitro characterization of the cytochrome P450 isoforms involved in the metabolism of 6-methoxy-2-napthylacetic acid, an active metabolite of the prodrug nabumetone. Biol Pharm Bull. 2011;34(5):734-9. [Article]

Details4. Corticosteroid 11-beta-dehydrogenase isozyme 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: 11-beta-hydroxysteroid dehydrogenase [nad(p)] activity
Specific Function: Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the rea...
Gene Name: HSD11B1
Uniprot ID: P28845
Uniprot Name: Corticosteroid 11-beta-dehydrogenase isozyme 1
Molecular Weight: 32400.665 Da

References

Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [Article]

Details5. Aldo-keto reductase family 1 member C1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function: Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the in...
Gene Name: AKR1C1
Uniprot ID: Q04828
Uniprot Name: Aldo-keto reductase family 1 member C1
Molecular Weight: 36788.02 Da

References

Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [Article]

Details6. Aldo-keto reductase family 1 member C2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function: Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent...
Gene Name: AKR1C2
Uniprot ID: P52895
Uniprot Name: Aldo-keto reductase family 1 member C2
Molecular Weight: 36734.97 Da

References

Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [Article]

Details7. Aldo-keto reductase family 1 member C4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Retinal dehydrogenase activity
Specific Function: Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid...
Gene Name: AKR1C4
Uniprot ID: P17516
Uniprot Name: Aldo-keto reductase family 1 member C4
Molecular Weight: 37066.52 Da

References

Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [Article]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Davies NM: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clin Pharmacokinet. 1997 Dec;33(6):404-16. doi: 10.2165/00003088-199733060-00001. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Nabumetone

Identification

Structure for Nabumetone (DB00461)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

Enzymes

References

References

References

References

References

References

References

Carriers

References