General
Preferred name
NABUMETONE
Synonyms
BRL14777 ()
BRL-14777 ()
BRL 14777 ()
Relafen ()
Relifex ()
NSC-758623 ()
Nabumetone-d3 ()
P&D ID
PD000963
CAS
42924-53-8
1216770-08-9
Tags
prodrug
natural product
drug
available
Approved by
FDA
First approval
1991
Drug Status
approved
Drug indication
Anti-Inflammatory
Pain
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma.[label,A178903] 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation.
INDICATION
**Indicated** for:[label]; ; 1) Symptomatic relief in rheumatoid arthritis.; ; 2) Symptomatic relief in osteoarthritis.
HALF-LIFE
6-MNA has a mean half-life of 24 hours with a range of 19-36 hours.[label]
METABOLISM
Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenase[A178897,A178900]. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite.[A17750,A178900] 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA).[A178897,A178900] Both 6-MNA and 6-HNA are further converted to conjugates.[A178900] 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.[A178972]
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,A178903] 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,L6466,A178903] Administration with food increases Cmax by 33% and increases absorption rate.[label,A178903] 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.[A178903]
DESCRIPTION
Nabumetone is a non-steroidal anti-inflammatory drug (NSAID). Nabumetone is a prodrug metabilosed to the active component, 6-methoxy-2-naphthylacetic acid (6MNA; CHEMBL1105)
(GtoPdb)
TOXICITY
**LD50 Values**; ; Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP)[L6565]; ; Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC)[L6565]; ; Monkey: 3200 mg/kg (Oral)[L6565]; ; **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,L6466] 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,L6466]] 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,L6466] 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.
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
23
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
44
Molecular Weight
228.12
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
4
Ring Count
2
Aromatic Ring Count
2
cLogP
3.37
TPSA
26.3
Fraction CSP3
0.27
Chiral centers
0.0
Largest ring
6.0
QED
0.8
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Immunology/Inflammation
Metabolism
Neuroscience
Target
COX-1
COX-2
MPO
PTGS1, PTGS2
COX
Indication
rheumatoid arthritis, osteoarthritis
MOA
cyclooxygenase inhibitor
Source data
