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

General Information of Drug (ID: DR2514)
Drug Name
Ketotifen
Synonyms
Ketotifen [INN:BAN]; Ketotifene; Ketotifene [INN-French]; Ketotifeno; Ketotifeno [INN-Spanish]; Ketotifenum; Ketotifenum [INN-Latin]; HC 20-511; ZCVMWBYGMWKGHF-UHFFFAOYSA-N; Zaditor; ketotifen; 34580-13-7; 4,9-Dihydro-4-(1-methyl-4-piperidinylidene)-10H-benzo(4,5)cyclohepta(1,2-b)thiophen-10-one; 4-(1-methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one; BRN 3983897; CHEMBL534; EINECS 252-099-7; HSDB 7283; UNII-X49220T18G
Indication Conjunctivitis [ICD11: 9A60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 309.4 Topological Polar Surface Area 48.6
Heavy Atom Count 22 Rotatable Bond Count 0
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
3827
ChEBI ID
CHEBI:92511
CAS Number
34580-13-7
Formula
C19H19NOS
Canonical SMILES
CN1CCC(=C2C3=C(C(=O)CC4=CC=CC=C42)SC=C3)CC1
InChI
1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3
InChIKey
ZCVMWBYGMWKGHF-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
10alpha-hydroxyl Ketotifen DM002829
323312
Reduction - Reduction 1 [5]
Ketotifen-N-glucuronide DM002828
131769917
Conjugation - N-Glucuronidation 1 [3] , [4]
Nor-ketotifen DM002831
9904236
Oxidation - N-Demethylation 1 [6] , [5]
10alpha-hydroxyl-demethylated Ketotifen DM002830
9904306
Unclear 2 [5]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001376 Ketotifen Ketotifen-N-glucuronide Conjugation - N-Glucuronidation UGT1A3 ... [3], [4]
MR001377 Ketotifen 10alpha-hydroxyl Ketotifen Reduction - Reduction Unclear [5]
MR001378 Ketotifen Nor-ketotifen Oxidation - N-Demethylation Unclear [6], [5]
MR001375 10alpha-hydroxyl Ketotifen 10alpha-hydroxyl-demethylated Ketotifen Unclear Unclear [5]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Short-chain dehydrogenase/reductase SDR19C1 (DHRS1) DME0628 Homo sapiens
DHRS1_HUMAN
1.1.1.-
[2]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 2B10 (UGT2B10) DME0205 Homo sapiens
UDB10_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 2B10 (UGT2B10) DME0205 Homo sapiens
UDB10_HUMAN
2.4.1.17
[4]
⏷ Show the Full List of 7  DME(s)
References
1 Ketotifen was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Initial characterization of human DHRS1 (SDR19C1), a member of the short-chain dehydrogenase/reductase superfamily. J Steroid Biochem Mol Biol. 2019 Jan;185:80-89.
3 N+-glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group Drug Metab Dispos. 1998 Sep;26(9):830-7.
4 Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97.
5 Quantification of ketotifen and its metabolites in human plasma by gas chromatography mass spectrometry Biomed Mass Spectrom. 1983 Mar;10(3):136-42. doi: 10.1002/bms.1200100307.
6 Ketotifen is a Prodrug. Norketotifen is the active metabolite Drug Dev Res. 2022 Apr;83(2):362-367. doi: 10.1002/ddr.21865.

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