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

General Information of Drug (ID: DR0488)
Drug Name
Diclofenac sodium
Synonyms
Delimon; Delphimix; Dichronic; Diclofenac (Sodium); Diclofenac sodium; Diclofenac sodium salt; Diclophenac sodium; Dyloject; EINECS 239-346-4; Feloran; GP 45840; Kriplex; Neriodin; Olfen; Orthophen; Ortofen; Prophenatin; Sodium (o-(2,6-dichloroanilino)phenyl)acetate; Sodium diclofenac; Tsudohmin; UNII-QTG126297Q; Urigon; Valetan; Voltaren ophthalmic; Voltarene; Vonafec; Vurdon; Diclofenac; Diclofenac acid; Diclofenac resinate; Diclofenaco; Diclofenaco [INN-Spanish]; Diclofenacum; Diclofenacum [INN-Latin]; Diclophenac; Novapirina; Pennsaid; ProSorb-D; UNII-144O8QL0L1; Voltaren; Voltarol; Dichlofenac; 15307-86-5; 2-((2,6-Dichlorophenyl)amino)benzeneacetic acid; 2-(2,6-Dichloroanilino)phenylacetic Acid; 2-(2-((2,6-Dichlorophenyl)amino)phenyl)acetic acid; 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid; Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-; CHEBI:47381; Cataflam; 15307-79-6; Allvoran; Anthraxiton; Assaren; Ba 47210; Batafil; Blesin; C14H10Cl2NNaO2; CCRIS 1909
Indication Osteoarthritis [ICD11: FA00] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 318.1 Topological Polar Surface Area 52.2
Heavy Atom Count 20 Rotatable Bond Count 4
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
5018304
ChEBI ID
CHEBI:4509
CAS Number
15307-79-6
TTD Drug ID
D0TG1H
Formula
C14H10Cl2NNaO2
Canonical SMILES
C1=CC=C(C(=C1)CC(=O)[O-])NC2=C(C=CC=C2Cl)Cl.[Na+]
InChI
1S/C14H11Cl2NO2.Na/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19;/h1-7,17H,8H2,(H,18,19);/q;+1/p-1
InChIKey
KPHWPUGNDIVLNH-UHFFFAOYSA-M
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'-hydroxydiclofenac DM000835
112230
Oxidation - 3'-Hydroxylation 1 [14] , [15]
4'-hydroxydiclofenac DM000838
116545
Oxidation - 4'-Hydroxylation 1 [16] , [14] , [15]
5-hydroxy diclofenac DM000841
3052566
Oxidation - 5-Hydroxylation 1 [14] , [15]
Diclofenac 2',3'-oxide DM000848
59831280
Unclear 1 [2]
Diclofenac acyl glucuronide DM000853
16084218
Conjugation - Glucuronidation 1 [2]
Diclofenac o-imine methine DM000846 N. A. Oxidation - Oxidative Decarboxylation 1 [2]
Diclofenac radical DM000851 N. A. Oxidation - Oxidation 1 [2]
2'-(glutathion-S-yl)-deschloro-diclofenac DM000852 N. A. Conjugation - Glutathione Conjugation 2 [2]
2'-hydroxy-3'-glutathione conjugated diclofenac DM000850 N. A. Conjugation - Glutathione Conjugation 2 [2]
2-(2,6-dichlorophenylamino)-benzyl-S-thioether glutathione DM000847 N. A. Conjugation - Glutathione Conjugation 2 [2]
3',4'-hydroxy diclofenac DM000836 N. A. Oxidation - 4'-Hydroxylation 2 [2]
3'-hydroxy-2'glutathione conjugated monoclofenac DM000849 N. A. Conjugation - Glutathione Conjugation 2 [2]
4',5-Dihydroxydiclofenac DM000844
3052567
Oxidation - Hydroxylation 2 [14]
4'-hydroxy-2'-glutathione conjugated monoclofenac DM000839
165340740
Conjugation - Glutathione Conjugation 2 [16]
4'-hydroxy-3'-glutathione conjugated diclofenac DM000840
100956536
Conjugation - Glutathione Conjugation 2 [2]
5,N-dihydroxy diclofenac DM000845
10065052
Oxidation - N-Hydroxylation 2 [2]
5-hydroxy-4-glutathione conjugated diclofenac DM000843
10095653
Conjugation - Glutathione Conjugation 2 [2]
5-hydroxy-6-glutathione conjugated diclofenac DM000842
100956537
Conjugation - Glutathione Conjugation 2 [2]
3'-hydroxy-4'-methoxy diclofenac DM000837
129615
Conjugation - O-Methylation 3 [2]
⏷ Show the Full List of 19  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002612 Diclofenac sodium 3'-hydroxydiclofenac Oxidation - 3'-Hydroxylation CYP2C9 [14], [15]
MR002613 Diclofenac sodium 4'-hydroxydiclofenac Oxidation - 4'-Hydroxylation CYP2C9 [16], [14], [15]
MR002614 Diclofenac sodium 5-hydroxy diclofenac Oxidation - 5-Hydroxylation CYP3A4 ... [14], [15]
MR002615 Diclofenac sodium Diclofenac o-imine methine Oxidation - Oxidative Decarboxylation Unclear [2]
MR002616 Diclofenac sodium Diclofenac 2',3'-oxide Unclear CYP2C9 [2]
MR002617 Diclofenac sodium Diclofenac radical Oxidation - Oxidation CYP3A4 [2]
MR002618 Diclofenac sodium Diclofenac acyl glucuronide Conjugation - Glucuronidation UGT2B7 ... [2]
MR002600 3'-hydroxydiclofenac 3',4'-hydroxy diclofenac Oxidation - 4'-Hydroxylation CYP2C9 [2]
MR002602 4'-hydroxydiclofenac 4'-hydroxy-2'-glutathione conjugated monoclofenac Conjugation - Glutathione Conjugation Unclear [16]
MR002603 4'-hydroxydiclofenac 4'-hydroxy-3'-glutathione conjugated diclofenac Conjugation - Glutathione Conjugation Unclear [2]
MR002604 5-hydroxy diclofenac 5-hydroxy-6-glutathione conjugated diclofenac Conjugation - Glutathione Conjugation Unclear [2]
MR002605 5-hydroxy diclofenac 5-hydroxy-4-glutathione conjugated diclofenac Conjugation - Glutathione Conjugation Unclear [2]
MR002606 5-hydroxy diclofenac 4',5-Dihydroxydiclofenac Oxidation - Hydroxylation CYP2C9 [14]
MR002607 5-hydroxy diclofenac 5,N-dihydroxy diclofenac Oxidation - N-Hydroxylation Unclear [2]
MR002609 Diclofenac 2',3'-oxide 3'-hydroxy-2'glutathione conjugated monoclofenac Conjugation - Glutathione Conjugation Unclear [2]
MR002610 Diclofenac 2',3'-oxide 2'-hydroxy-3'-glutathione conjugated diclofenac Conjugation - Glutathione Conjugation Unclear [2]
MR002608 Diclofenac o-imine methine 2-(2,6-dichlorophenylamino)-benzyl-S-thioether glutathione Conjugation - Glutathione Conjugation Unclear [2]
MR002611 Diclofenac radical 2'-(glutathion-S-yl)-deschloro-diclofenac Conjugation - Glutathione Conjugation GSTP1 [2]
MR002601 3',4'-hydroxy diclofenac 3'-hydroxy-4'-methoxy diclofenac Conjugation - O-Methylation COMT [2]
⏷ Show the Full List of 19 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Catechol O-methyltransferase (COMT) DME0043 Homo sapiens
COMT_HUMAN
2.1.1.6
[2]
Cholesterol 24-hydroxylase (CYP46A1) DME0028 Homo sapiens
CP46A_HUMAN
1.14.14.25
[3]
Cytochrome P450 102A1 (cyp102) DME1075 Bacillus megaterium
CPXB_BACMB
1.14.14.1
[4]
Cytochrome P450 105D7 (cyp105) DME1233 Streptomyces avermitilis
CYP28_STRAW
1.14.15.11
[4]
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[5]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[6]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[7]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[8]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[9]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[10]
Glutathione S-transferase pi (GSTP1) DME0088 Homo sapiens
GSTP1_HUMAN
2.5.1.18
[2]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[5]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[11]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[11]
UDP-glucuronosyltransferase 2B4 (UGT2B4) DME0047 Homo sapiens
UD2B4_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[12]
⏷ Show the Full List of 17  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
Cytochrome P450 105D7 (cyp105) DME1233 Kcat/Km = 0.15 s-1microM-1
CYP28_STRAW
[13] , [4]
References
1 Diclofenac Sodium was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 DrugBank(Pharmacology-Metabolism)Diclofenac sodium
3 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
4 Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis. J Microbiol Biotechnol. 2017 May 28;27(5):956-964.
5 Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
6 Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
7 Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
8 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
9 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
10 Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine. Drug Metab Dispos. 2000 Sep;28(9):1043-50.
11 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
12 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.
13 The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
14 Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis Eur J Clin Pharmacol. 1983;25(3):389-94. doi: 10.1007/BF01037953.
15 Simultaneous determination of diclofenac sodium and its hydroxy metabolites by capillary column gas chromatography with electron-capture detection J Chromatogr. 1981 Nov 6;217:263-71. doi: 10.1016/s0021-9673(00)88081-4.
16 Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls Clin Pharmacokinet. 1997 Sep;33(3):184-213. doi: 10.2165/00003088-199733030-00003.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.