Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1122)
Drug Name
Nabumetone
Prodrug Info Nabumetone is the prodrug of 6-methoxy-2-naphthylacetic acid
Synonyms
Nabumetona; Nabumetonum; Nabumetonum [INN-Latin]; Nabuser; Prodac; Relafen; Relifen; Relifex; Unimetone; nabumeton; nabumetone; Arthaxan; Balmox; Consolan; Dolsinal; Flambate; LW0TIW155Z; Listran; Mebutan; 2-Butanone, 4-(6-methoxy-2-naphthalenyl)-; 4-(2-Methoxynaphthalen-6-yl)butan-2-one; 4-(6-Methoxy-2-naphthalenyl)-2-butanone; 4-(6-Methoxy-2-naphthyl)-2-butanone; 4-(6-methoxynaphthalen-2-yl)butan-2-one; 42924-53-8; BRL 14777; BRL-14777; BRN 2103472; CHEBI:7443; MLS000069541; Relif; SMR000058835; UNII-LW0TIW155Z
Indication Rheumatoid arthritis [ICD11: FA20] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 228.29 Topological Polar Surface Area 26.3
Heavy Atom Count 17 Rotatable Bond Count 4
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
4409
PubChem SID
866759 ; 5089100 ; 7847491 ; 7980058 ; 8139968 ; 8150030 ; 8152727 ; 11112767 ; 11336025 ; 11361264 ; 11364380 ; 11366942 ; 11369504 ; 11373826 ; 11377666 ; 11462236 ; 11466937 ; 11468057 ; 11485833 ; 11486693 ; 11489785 ; 11491989 ; 11495300 ; 12012677 ; 15196152 ; 24897772 ; 26612514 ; 26679665 ; 26748824 ; 26748825 ; 29223506 ; 46507729 ; 47216826 ; 47515367 ; 47662339 ; 47736536 ; 47885464 ; 48035181 ; 49698816 ; 49896758 ; 53786809 ; 56364587 ; 56422157 ; 57322259 ; 57654458 ; 80932204 ; 85087976 ; 85787391 ; 92124694 ; 92125724
ChEBI ID
CHEBI:7443
CAS Number
42924-53-8
TTD Drug ID
D05CKR
Formula
C15H16O2
Canonical SMILES
CC(=O)CCC1=CC2=C(C=C1)C=C(C=C2)OC
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
InChIKey
BLXXJMDCKKHMKV-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
3-OH-nabumetone DM004497
20502764
Oxidation - Hydrolyzationn 1 [2] , [5] , [6] , [3] , [7]
4-(6-Hydroxy-2-naphthyl)- butan-2-one DM004509
71374602
Oxidation - O-demethylation 1 [6]
4-(6-Methoxy-2-naphthyl)- butan-2-ol DM004503
10911373
Reduction - Reduction 1 [6]
4-(6-hydroxy-2-naphthyl)- butan-2-ol DM004504
19933739
Unclear 2 [6]
4-(6-hydroxy-2-naphthyl)- butan-2-ol DM004504
19933739
Reduction - Reduction 2 [6]
4-(6-Hydroxy-2-naphthyl)- butan-2-one glucuronide DM004516 N. A. Conjugation - O-glucuronidation 2 [6]
4-(6-Hydroxy-2-naphthyl)- butan-2-one sulfate DM004519 N. A. Conjugation - Sulfonation 2 [6]
4-(6-Methoxy-2-naphthyl)- butan-2-ol glucuronide DM004518 N. A. Conjugation - O-glucuronidation 2 [6]
6-methoxy-2-naphthylacetic acid DM004510
32176
Oxidation - Dealkylation 2 [6]
O-desmethyl-3-hydroxy-nabumetone DM004498
118753584
Oxidation - O-demethylation 2 [5]
Reduced 3-hydroxy-nabumetone DM004502 N. A. Reduction - Reduction 2 [5]
4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (2-OH conjugated) DM004505 N. A. Conjugation - O-glucuronidation 3 [6]
4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (6-OH conjugated) DM004507 N. A. Conjugation - O-glucuronidation 3 [6]
4-(6-hydroxy-2-naphthyl)- butan-2-ol sulfate DM004515 N. A. Conjugation - Sulfonation 3 [6]
4-(6-Hydroxy-2-naphthyl)- butan-2-one glucuronide glycine conjugate DM004517 N. A. Conjugation - Glycine conjugation 3 [6]
6-hydroxy-naphthylacetic acid DM004511 N. A. Oxidation - O-demethylation 3 [6]
6-methoxy-naphthylacetic acid glucuronide DM004514 N. A. Conjugation - O-glucuronidation 3 [6]
Reduced O-desmethyl-3-hydroxy-nabumetone DM004499
118753585
Reduction - Reduction 3 [5]
Reduced O-desmethyl-3-hydroxy-nabumetone DM004499
118753585
Oxidation - O-demethylation 3 [5]
4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (2-OH conjugated) glycine conjugate DM004506 N. A. Conjugation - Glycine conjugation 4 [6]
4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (6-OH conjugated) glycine conjugate DM004508 N. A. Conjugation - Glycine conjugation 4 [6]
6-hydroxy-naphthylacetic acid glucuronide DM004513 N. A. Conjugation - O-glucuronidation 4 [6]
6-hydroxy-naphthylacetic acid sulfate DM004512 N. A. Conjugation - Sulfonation 4 [6]
Reduced O-desmethyl-3-hydroxy-nabumetone glucuronide DM004500 N. A. Conjugation - O-glucuronidation 4 [5]
Reduced O-desmethyl-3-hydroxy-nabumetone glucuronide glycine conjugate DM004501 N. A. Conjugation - Glycine conjugation 5 [5]
⏷ Show the Full List of 25  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004825 Nabumetone 3-OH-nabumetone Oxidation - Hydrolyzationn HSD11B1 ... [2], [5], [6], [3], [7]
MR004832 Nabumetone 4-(6-Methoxy-2-naphthyl)- butan-2-ol Reduction - Reduction Unclear [6]
MR004838 Nabumetone 4-(6-Hydroxy-2-naphthyl)- butan-2-one Oxidation - O-demethylation Unclear [6]
MR004826 3-OH-nabumetone O-desmethyl-3-hydroxy-nabumetone Oxidation - O-demethylation Unclear [5]
MR004830 3-OH-nabumetone Reduced 3-hydroxy-nabumetone Reduction - Reduction Unclear [5]
MR004840 3-OH-nabumetone 6-methoxy-2-naphthylacetic acid Oxidation - Dealkylation CYP1A2 [6]
MR004839 4-(6-Hydroxy-2-naphthyl)- butan-2-one 4-(6-hydroxy-2-naphthyl)- butan-2-ol Reduction - Reduction Unclear [6]
MR004846 4-(6-Hydroxy-2-naphthyl)- butan-2-one 4-(6-Hydroxy-2-naphthyl)- butan-2-one glucuronide Conjugation - O-glucuronidation Unclear [6]
MR004849 4-(6-Hydroxy-2-naphthyl)- butan-2-one 4-(6-Hydroxy-2-naphthyl)- butan-2-one sulfate Conjugation - Sulfonation Unclear [6]
MR004833 4-(6-Methoxy-2-naphthyl)- butan-2-ol 4-(6-hydroxy-2-naphthyl)- butan-2-ol Unclear Unclear [6]
MR004848 4-(6-Methoxy-2-naphthyl)- butan-2-ol 4-(6-Methoxy-2-naphthyl)- butan-2-ol glucuronide Conjugation - O-glucuronidation Unclear [6]
MR004834 4-(6-hydroxy-2-naphthyl)- butan-2-ol 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (2-OH conjugated) Conjugation - O-glucuronidation Unclear [6]
MR004836 4-(6-hydroxy-2-naphthyl)- butan-2-ol 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (6-OH conjugated) Conjugation - O-glucuronidation Unclear [6]
MR004845 4-(6-hydroxy-2-naphthyl)- butan-2-ol 4-(6-hydroxy-2-naphthyl)- butan-2-ol sulfate Conjugation - Sulfonation Unclear [6]
MR004847 4-(6-Hydroxy-2-naphthyl)- butan-2-one glucuronide 4-(6-Hydroxy-2-naphthyl)- butan-2-one glucuronide glycine conjugate Conjugation - Glycine conjugation Unclear [6]
MR004841 6-methoxy-2-naphthylacetic acid 6-hydroxy-naphthylacetic acid Oxidation - O-demethylation Unclear [6]
MR004844 6-methoxy-2-naphthylacetic acid 6-methoxy-naphthylacetic acid glucuronide Conjugation - O-glucuronidation Unclear [6]
MR004827 O-desmethyl-3-hydroxy-nabumetone Reduced O-desmethyl-3-hydroxy-nabumetone Reduction - Reduction Unclear [5]
MR004831 Reduced 3-hydroxy-nabumetone Reduced O-desmethyl-3-hydroxy-nabumetone Oxidation - O-demethylation Unclear [5]
MR004835 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (2-OH conjugated) 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (2-OH conjugated) glycine conjugate Conjugation - Glycine conjugation Unclear [6]
MR004837 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (6-OH conjugated) 4-(6-hydroxy-2-naphthyl)- butan-2-ol glucuronide (6-OH conjugated) glycine conjugate Conjugation - Glycine conjugation Unclear [6]
MR004842 6-hydroxy-naphthylacetic acid 6-hydroxy-naphthylacetic acid sulfate Conjugation - Sulfonation Unclear [6]
MR004843 6-hydroxy-naphthylacetic acid 6-hydroxy-naphthylacetic acid glucuronide Conjugation - O-glucuronidation Unclear [6]
MR004828 Reduced O-desmethyl-3-hydroxy-nabumetone Reduced O-desmethyl-3-hydroxy-nabumetone glucuronide Conjugation - O-glucuronidation Unclear [5]
MR004829 Reduced O-desmethyl-3-hydroxy-nabumetone glucuronide Reduced O-desmethyl-3-hydroxy-nabumetone glucuronide glycine conjugate Conjugation - Glycine conjugation Unclear [5]
⏷ Show the Full List of 25 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Aldo-keto reductase 1C1 (AKR1C1) DME0197 Homo sapiens
AK1C1_HUMAN
1.1.1.149
[2]
Aldo-keto reductase 1C4 (AKR1C4) DME0198 Homo sapiens
AK1C4_HUMAN
1.1.1.357
[2]
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1) DME0199 Homo sapiens
DHI1_HUMAN
1.1.1.146
[2]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
References
1 Nabumetone was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 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.
3 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.
4 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.
5 Analytical power of LLE-HPLC-PDA-MS/MS in drug metabolism studies: identification of new nabumetone metabolites
6 Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition?
7 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

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