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

General Information of Drug (ID: DR1444)
Drug Name
Rosiglitazone
Synonyms
Rosigilitazone; Rosiglitazone [INN:BAN]; Rosiglitazone maleate; Rosiglizole; TDZ 01; YASAKCUCGLMORW-UHFFFAOYSA-N; Avandamet; Avandaryl; Avandia; rosiglitazona; rosiglitazone; rosiglitazone (Avandia); rosiglitazonum; 122320-73-4; 5-((4-(2-Methyl-2-(pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione-2-butenedioate; 5-(4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione; 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione; BRL49653; Brl 49653; Brl-49653; C18H19N3O3S; CHEBI:50122
Indication Diabetes mellitus [ICD11: 5A10] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 357.4 Topological Polar Surface Area 96.8
Heavy Atom Count 25 Rotatable Bond Count 7
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
77999
ChEBI ID
CHEBI:50122
CAS Number
122320-73-4
Formula
C18H19N3O3S
Canonical SMILES
CN(CCOC1=CC=C(C=C1)CC2C(=O)NC(=O)S2)C3=CC=CC=N3
InChI
1S/C18H19N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,15H,10-12H2,1H3,(H,20,22,23)
InChIKey
YASAKCUCGLMORW-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
N-Desmethylrosiglitazone DM015794
12000328
Oxidation - N-demethylation 1 [6]
N-Desmethylrosiglitazone DM015794
12000328
Oxidation - N-demethylation 1 [7]
N-Despyridinyl rosiglitazone DM015657
10356320
Unclear - Unclear 1 [6]
Ortho-Hydroxyrosiglitazone DM016443
100995317
Oxidation - Hydroxylation 1 [6]
Para-Hydroxyrosiglitazone DM015545
9864316
Oxidation - Hydroxylation 1 [6]
Para-Hydroxyrosiglitazone DM015545
9864316
Oxidation - Hydroxylation 1 [7]
Phenoxyacetic acid derivative of rosiglitazone DM015750
11323485
Oxidation - N-oxidation 1 [6]
N-Desmethyl glucuronide rosiglitazone DM016860
165361837
Conjugation - Glucuronidation 2 [8]
N-Desmethyl-ortho-hydroxy rosiglitazone DM016382
86278298
Oxidation - N-demethylation 2 [6]
N-Desmethyl-ortho-hydroxy rosiglitazone DM016382
86278298
Oxidation - Hydroxylation 2 [6]
N-Desmethyl-para-hydroxy rosiglitazone DM016592
131769972
Oxidation - N-demethylation 2 [6]
N-Desmethyl-para-hydroxy rosiglitazone DM016592
131769972
Oxidation - Hydroxylation 2 [6]
Ortho-O-Glucuronide rosiglitazone DM017925 N. A. Conjugation - Glucuronidation 2 [6]
Ortho-O-Sulfate rosiglitazone DM016594
131769978
Oxidation - Sulfonation 2 [6]
Para-O-Glucuronide rosiglitazone DM017924 N. A. Conjugation - Glucuronidation 2 [6]
Para-O-Sulfate rosiglitazone DM015538
9846723
Oxidation - Sulfonation 2 [6]
N-Desmethyl para-O-sulfate rosiglitazone DM016593
131769973
Oxidation - Sulfonation 3 [6]
N-Desmethyl-ortho-O-sulfate rosiglitazone DM016591
131769971
Oxidation - Sulfonation 3 [6]
⏷ Show the Full List of 18  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009576 Rosiglitazone N-Desmethylrosiglitazone Oxidation - N-demethylation CYP2C8 ... [6]
MR009582 Rosiglitazone Para-Hydroxyrosiglitazone Oxidation - Hydroxylation CYP2C8 ... [6]
MR009586 Rosiglitazone Ortho-Hydroxyrosiglitazone Oxidation - Hydroxylation CYP2C8 ... [6]
MR009590 Rosiglitazone N-Despyridinyl rosiglitazone Unclear - Unclear Unclear [6]
MR009591 Rosiglitazone Phenoxyacetic acid derivative of rosiglitazone Oxidation - N-oxidation Unclear [6]
MR009577 N-Desmethylrosiglitazone N-Desmethyl-para-hydroxy rosiglitazone Oxidation - Hydroxylation Unclear [6]
MR009579 N-Desmethylrosiglitazone N-Desmethyl-ortho-hydroxy rosiglitazone Oxidation - Hydroxylation Unclear [6]
MR009581 N-Desmethylrosiglitazone N-Desmethyl glucuronide rosiglitazone Conjugation - Glucuronidation Unclear [8]
MR009587 Ortho-Hydroxyrosiglitazone N-Desmethyl-ortho-hydroxy rosiglitazone Oxidation - N-demethylation Unclear [6]
MR009588 Ortho-Hydroxyrosiglitazone Ortho-O-Sulfate rosiglitazone Oxidation - Sulfonation Unclear [6]
MR009589 Ortho-Hydroxyrosiglitazone Ortho-O-Glucuronide rosiglitazone Conjugation - Glucuronidation Unclear [6]
MR009583 Para-Hydroxyrosiglitazone N-Desmethyl-para-hydroxy rosiglitazone Oxidation - N-demethylation Unclear [6]
MR009584 Para-Hydroxyrosiglitazone Para-O-Sulfate rosiglitazone Oxidation - Sulfonation Unclear [6]
MR009585 Para-Hydroxyrosiglitazone Para-O-Glucuronide rosiglitazone Conjugation - Glucuronidation Unclear [6]
MR009580 N-Desmethyl-ortho-hydroxy rosiglitazone N-Desmethyl-ortho-O-sulfate rosiglitazone Oxidation - Sulfonation Unclear [6]
MR009578 N-Desmethyl-para-hydroxy rosiglitazone N-Desmethyl para-O-sulfate rosiglitazone Oxidation - Sulfonation Unclear [6]
⏷ Show the Full List of 16 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[6]
⏷ Show the Full List of 8  DME(s)
References
1 Rosiglitazone was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol. 1999 Sep;48(3):424-32.
3 Rosiglitazone Metabolism in Human Liver Microsomes Using a Substrate Depletion Method
4 DrugBank(Pharmacology-Metabolism):Rosiglitazone
5 Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14.
6 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.
7 Simultaneous quantification of rosiglitazone and its two major metabolites, N-desmethyl and p-hydroxy rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study
8 Pharmacogenomics knowledge for personalized medicine Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.

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