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

General Information of Drug (ID: DR1613)
Drug Name
GEA-6414
Synonyms
Tolfenamic acid; Acide tolfenamique; Acido tolfenamico; Acidum tolfenamicum; Bifenac; Clotam; GEA 6414; Tolfedine; tolfenamic acid; 13710-19-5; 2-(3-Chloro-2-methylanilino)benzoic acid; 2-[(3-Chloro-2-methylphenyl)amino]benzoic Acid; 3G943U18KM; Anthranilic acid, N-(3-chloro-o-tolyl)-; Benzoic acid, 2-[(3-chloro-2-methylphenyl)amino]-; CAS-13710-19-5; CHEBI:32243; N-(2-Methyl-3-chlorophenyl)anthranilic acid; N-(3-Chloro-2-methylphenyl)anthranilic acid; N-(3-Chloro-o-tolyl)-anthranilic acid; NCGC00016705-05; UNII-3G943U18KM
Indication Parkinsonism [ICD11: 8A00] Phase 1/2 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 261.7 Topological Polar Surface Area 49.3
Heavy Atom Count 18 Rotatable Bond Count 3
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
610479
ChEBI ID
CHEBI:32243
CAS Number
13710-19-5
Formula
C14H12ClNO2
Canonical SMILES
CC1=C(C=CC=C1Cl)NC2=CC=CC=C2C(=O)O
InChI
1S/C14H12ClNO2/c1-9-11(15)6-4-8-12(9)16-13-7-3-2-5-10(13)14(17)18/h2-8,16H,1H3,(H,17,18)
InChIKey
YEZNLOUZAIOMLT-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
Ether glucuronide ofN-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid DM005742 N. A. Conjugation - Glucuronidation 1 [5]
Glucuronide form of tolfenamic acid DM005740 N. A. Conjugation - Glucuronidation 1 [5]
N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid DM005735
53703
Multi-steps Reaction - Glucuronidation; hydroxylation 1 [5]
N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid DM005730
53704
Oxidation - 4-hydroxylation 1 [4]
N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid DM005730
53704
Multi-steps Reaction - Glucuronidation; hydroxylation 1 [5]
N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid DM005743
15817775
Conjugation - O-glucuronidation 1 [5]
N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid form 2 DM005733 N. A. Multi-steps Reaction - Glucuronidation; hydroxylation 1 [5]
N-(2-methyl-3-chlorophenyl)-4-hydroxy-anthranilic acid DM005744 N. A. Multi-steps Reaction - Glucuronidation; hydroxylation 1 [5]
N-(2-methyl-3-chlorophenyl)-5-hydroxy-anthranilic acid DM005741 N. A. Multi-steps Reaction - Glucuronidation; hydroxylation 1 [5]
N-(2-carboxy-3-chlorophenyl)-anthranilic acid DM005736 N. A. Oxidation - Hydrolyzationn 2 [5]
N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid DM005738
54543233
Oxidation - Hydrolyzationn; oxidation 2 [5]
N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic DM005737
15817774
Oxidation - Hydrolyzationn; oxidation 2 [5]
N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic acid DM005732 N. A. Oxidation - Hydrolyzationn; oxidation 2 [5]
N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic acid DM005732 N. A. Reduction - Dehalogenation 2 [5]
N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid form 3 DM005734 N. A. Conjugation - Glucuronidation 2 [5]
N-(2-methyl-4-hydroxyphenyl)-anthranilic acid DM005731 N. A. Reduction - Dehalogenation 2 [5]
⏷ Show the Full List of 16  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006114 GEA-6414 N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid Multi-steps Reaction - Glucuronidation; hydroxylation CYP3A4 [5]
MR006117 GEA-6414 N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid form 2 Multi-steps Reaction - Glucuronidation; hydroxylation CYP3A4 [5]
MR006119 GEA-6414 N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid Multi-steps Reaction - Glucuronidation; hydroxylation CYP3A4 [5]
MR006124 GEA-6414 Glucuronide form of tolfenamic acid Conjugation - Glucuronidation Unclear [5]
MR006125 GEA-6414 N-(2-methyl-3-chlorophenyl)-5-hydroxy-anthranilic acid Multi-steps Reaction - Glucuronidation; hydroxylation CYP3A4 [5]
MR006126 GEA-6414 Ether glucuronide ofN-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid Conjugation - Glucuronidation Unclear [5]
MR006127 GEA-6414 N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid Conjugation - O-glucuronidation Unclear [5]
MR006128 GEA-6414 N-(2-methyl-3-chlorophenyl)-4-hydroxy-anthranilic acid Multi-steps Reaction - Glucuronidation; hydroxylation CYP3A4 [5]
MR006120 N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid N-(2-carboxy-3-chlorophenyl)-anthranilic acid Oxidation - Hydrolyzationn Unclear [5]
MR006121 N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic Oxidation - Hydrolyzationn; oxidation Unclear [5]
MR006122 N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid Oxidation - Hydrolyzationn; oxidation Unclear [5]
MR006123 N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic acid Oxidation - Hydrolyzationn; oxidation Unclear [5]
MR006115 N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid N-(2-methyl-4-hydroxyphenyl)-anthranilic acid Reduction - Dehalogenation Unclear [5]
MR006116 N-(2-methyl-3-chloro-4-hydroxyphenyl)-anthranilic acid N-(2-methyl-3-chloro-4-metoxyphenyl)-anthranilic acid Reduction - Dehalogenation Unclear [5]
MR006118 N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid form 2 N-(2-methyl-3-chloro-5-hydroxyphenyl)-anthranilic acid form 3 Conjugation - Glucuronidation Unclear [5]
⏷ 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
Cytochrome P450 102A1 (cyp102) DME1075 Bacillus megaterium
CPXB_BACMB
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Vitamin D3 dihydroxylase (cyp105A1) DMEN027 Streptomyces griseolus
CPXE_STRGO
Not Available [4]
References
1 ClinicalTrials.gov (NCT04253132) Evaluation of Tolfenamic Acid in Individuals With PSP at 12-Weeks.
2 Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of fenamic acids in BM3 mutants. J Chem Inf Model. 2019 Feb 25;59(2):743-753.
3 Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
4 Metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) by Streptomyces griseolus CYP105A1 and its variants Drug Metab Pharmacokinet. 2022 Aug;45:100455. doi: 10.1016/j.dmpk.2022.100455.
5 Purification and 1H NMR spectroscopic characterization of phase II metabolites of tolfenamic acid

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