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

General Information of Drug (ID: DR1130)
Drug Name
Naproxen
Synonyms
Nafasol; Naixan; Nalyxan; Napflam; Napmel; Naposin; Napren; Naprius; Naprosyn; Naprosyne; Naproxene; Naproxeno; Naproxenum; Novonaprox; Nycopren; Reuxen; d-Naproxen; (+)-(S)-Naproxen; (+)-Naproxen; (S)-(+)-2-(6-Methoxy-2-naphthyl)propionic acid; Acusprain; Anexopen; Apronax; Artagen; Arthrisil; Artrixen; Artroxen; Atiflan; Bipronyl; Calosen; Clinosyn; Danaprox; Daprox; Ec-Naprosyn; Equiproxen; Flexipen; Genoxen; Laraflex; Leniartil; NAPROXEN; (S)-(+)-Naproxen; (S)-2-(6-methoxynaphthalen-2-yl)propanoic acid; (S)-Naproxen; 22204-53-1; Aleve; Axer; Bonyl
Indication Rheumatoid arthritis [ICD11: FA20] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 230.26 Topological Polar Surface Area 46.5
Heavy Atom Count 17 Rotatable Bond Count 3
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
156391
PubChem SID
4682 ; 597410 ; 3248704 ; 7847186 ; 7980083 ; 8149438 ; 10252902 ; 10321400 ; 11112669 ; 11335417 ; 11360656 ; 11363871 ; 11366433 ; 11368995 ; 11371667 ; 11373736 ; 11377157 ; 11461628 ; 11466819 ; 11467939 ; 11484702 ; 11486597 ; 11488859 ; 11490330 ; 11491884 ; 11494791 ; 15172373 ; 15172374 ; 22391409 ; 24857178 ; 24870224 ; 24883816 ; 24897861 ; 25649496 ; 26527900 ; 26611833 ; 26679674 ; 26755231 ; 46232210 ; 46487915 ; 46505508 ; 47291026 ; 47588882 ; 47810639 ; 48334369 ; 48334370 ; 48426145 ; 49833549 ; 50025704 ; 50103854
ChEBI ID
CHEBI:7476
CAS Number
22204-53-1
TTD Drug ID
D0DJ1B
Formula
C14H14O3
Canonical SMILES
CC(C1=CC2=C(C=C1)C=C(C=C2)OC)C(=O)O
InChI
1S/C14H14O3/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10/h3-9H,1-2H3,(H,15,16)/t9-/m0/s1
InChIKey
CMWTZPSULFXXJA-VIFPVBQESA-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
Naproxen metabolite M1 DM003064
135398638
Oxidation - Hydrolyzationn 1 [2]
Naproxen O-glucuronide DM004546
54484412
Conjugation - Glucuronidation 1 [7]
O-Desmethylnaproxen DM004542
13393711
Oxidation - O-demethylation 1 [5] , [3] , [7] , [9]
Naproxen metabolite M2 DM004535 N. A. Unclear 2 [2]
O-Desmethylnaproxen acyl glucuronide DM004544 N. A. Conjugation - Glucuronidation 2 [5]
O-Desmethylnaproxen O-glucuronide DM004543 N. A. Conjugation - Glucuronidation 2 [5]
O-Desmethylnaproxen sulfate DM004545
184679
Conjugation - Sulfonation 2 [5]
Naproxen metabolite M3 DM004536 N. A. Unclear 3 [2]
Naproxen metabolite M4 DM004537 N. A. Unclear 4 [2]
5-methoxysalicylaldehyde DM004538
95695
Unclear 5 [2]
5-methoxysalicylic acid DM004539
75787
Unclear 6 [2]
Catechol DM003935
289
Multi-steps Reaction - Demethylation; Reduction 7 [2]
Gentistic acid DM001774
3469
Multi-steps Reaction - Demethylation; Reduction 7 [2]
Cis-cis muconic acid DM004540
5280518
Unclear 8 [2]
Maleylpyruate DM004541
5280494
Unclear 8 [2]
⏷ Show the Full List of 15  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004861 Naproxen Naproxen metabolite M1 Oxidation - Hydrolyzationn doxB [2]
MR004871 Naproxen O-Desmethylnaproxen Oxidation - O-demethylation CYP2C9 ... [5], [3], [7], [9]
MR004875 Naproxen Naproxen O-glucuronide Conjugation - Glucuronidation Unclear [7]
MR004862 Naproxen metabolite M1 Naproxen metabolite M2 Unclear Unclear [2]
MR004872 O-Desmethylnaproxen O-Desmethylnaproxen O-glucuronide Conjugation - Glucuronidation UGT1A1 ... [5]
MR004873 O-Desmethylnaproxen O-Desmethylnaproxen acyl glucuronide Conjugation - Glucuronidation UGT1A1 ... [5]
MR004874 O-Desmethylnaproxen O-Desmethylnaproxen sulfate Conjugation - Sulfonation SULT1A1 ... [5]
MR004863 Naproxen metabolite M2 Naproxen metabolite M3 Unclear Unclear [2]
MR004864 Naproxen metabolite M3 Naproxen metabolite M4 Unclear AMACR [2]
MR004865 Naproxen metabolite M4 5-methoxysalicylaldehyde Unclear Unclear [2]
MR004866 5-methoxysalicylaldehyde 5-methoxysalicylic acid Unclear Unclear [2]
MR004867 5-methoxysalicylic acid Catechol Multi-steps Reaction - Demethylation; Reduction cyp51A [2]
MR004869 5-methoxysalicylic acid Gentistic acid Multi-steps Reaction - Demethylation; Reduction cyp51A [2]
MR004868 Catechol Cis-cis muconic acid Unclear catA [2]
MR004870 Gentistic acid Maleylpyruate Unclear gdoA [2]
⏷ Show the Full List of 15 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Alpha-methylacyl-CoA racemase (AMACR) DME0116 Homo sapiens
AMACR_HUMAN
5.1.99.4
[2]
Catechol 1,2-dioxygenase (catA) DMEN385 . Not Available Not Available [2]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 monooxygenase 51A (cyp51A) DME1664 Aspergillus fumigatus
CP51A_ASPFU
1.14.14.154
[2]
Gentisate 1,2-dioxygenase (gdoA) DMEN386 . Not Available Not Available [2]
Naphthalene dioxygenase (doxB) DME1615 Pseudomonas furukawaii
NDOB_PSEU8
1.14.12.12
[2]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[5]
Sulfotransferase 1B1 (SULT1B1) DME0380 Homo sapiens
ST1B1_HUMAN
2.8.2.1
[5]
Sulfotransferase 1E1 (SULT1E1) DME0061 Homo sapiens
ST1E1_HUMAN
2.8.2.4
[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[6]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DME0075 Homo sapiens
UD110_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Homo sapiens
UD16_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A7 (UGT1A7) DME0065 Homo sapiens
UD17_HUMAN
2.4.1.17
[5]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[5]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [8]
⏷ Show the Full List of 25  DME(s)
References
1 Naproxen was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway
3 Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol. 1997;52(4):293-8.
4 Drug interactions in dentistry: the importance of knowing your CYPs. J Am Dent Assoc. 2004 Mar;135(3):298-311.
5 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
6 Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet Genomics. 2007 Dec;17(12):1017-29.
7 S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33.
8 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
9 [Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]

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