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

General Information of Drug (ID: DR1651)
Drug Name
Troglitazone
Synonyms
Troglitazone (CS-045); troglitazone; (+-)-all-rac-5-(p-((6-Hydroxy-2,5,7,8-tetramethyl-2-chromanyl)methoxy)benzyl)-2,4-thiazolidinedione; Noscal; Prelay; Rezulin; Rezulin (TN); Romglizone; Romozin; 5-(4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)benzyl)thiazolidine-2,4-dione; 97322-87-7; BRN 4338399; C24H27NO5S; CCRIS 8969; CHEBI:9753; CI 991; CI-991; CS 045; CS-045; CS045; GR 92132X; GR-92132X; GR92132X; GXPHKUHSUJUWKP-UHFFFAOYSA-N
Indication Diabetes mellitus [ICD11: 5A10] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 441.5 Topological Polar Surface Area 110
Heavy Atom Count 31 Rotatable Bond Count 5
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
5591
PubChem SID
841060 ; 4894294 ; 7847461 ; 7980843 ; 8153443 ; 11533348 ; 12013560 ; 14905963 ; 22391425 ; 24724629 ; 26681461 ; 26755242 ; 26755243 ; 26757864 ; 26759664 ; 29216382 ; 29224629 ; 46487963 ; 46504655 ; 47365443 ; 47811013 ; 48035383 ; 48416678 ; 50052241 ; 53788686 ; 56311256 ; 56312004 ; 56313972 ; 56313996 ; 57288866 ; 57322861 ; 74940595 ; 85246179 ; 85257254 ; 85787118 ; 91011836 ; 92307894 ; 92308758 ; 103164301 ; 103853949 ; 104309674 ; 104829539 ; 119526104 ; 124892345 ; 124892346 ; 124892347 ; 124892348 ; 125334732 ; 126647230 ; 126683373
ChEBI ID
ChEBI:9753
CAS Number
97322-87-7
TTD Drug ID
D06XZW
Formula
C24H27NO5S
Canonical SMILES
CC1=C(C2=C(CCC(O2)(C)COC3=CC=C(C=C3)CC4C(=O)NC(=O)S4)C(=C1O)C)C
InChI
1S/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28)
InChIKey
GXPHKUHSUJUWKP-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
Troglitazone glucuronide metabolite DM002404
15670672
Conjugation - Glucuronidation 1 [9] , [7]
Troglitazone Quinone DM002405
9911974
Oxidation - Oxidation 1 [2] , [10]
Troglitazone sulfate metabolite DM002403
10229833
Conjugation - Sulfation 1 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002464 Troglitazone Troglitazone sulfate metabolite Conjugation - Sulfation Unclear [9]
MR002465 Troglitazone Troglitazone glucuronide metabolite Conjugation - Glucuronidation UGT1A1 ... [9], [7]
MR002466 Troglitazone Troglitazone Quinone Oxidation - Oxidation CYP2C8 ... [2], [10]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2]
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 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Glutathione S-transferase (GST) DMEN072 . Not Available Not Available [5]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[4]
Sulfotransferase (SULT) DMEN061 . Not Available Not Available [6]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[7]
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 1A8 (UGT1A8) DME0064 Homo sapiens
UD18_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[7]
UDP-glucuronyltransferase (UGT) DMEN064 . Not Available Not Available [5]
⏷ Show the Full List of 15  DME(s)
References
1 Troglitazone was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes. Drug Metab Dispos. 1999 Nov;27(11):1260-6.
3 Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance. Clin Pharmacokinet. 2005;44(12):1209-25.
4 In vitro inhibitory effects of troglitazone and its metabolites on drug oxidation activities of human cytochrome P450 enzymes: comparison with pioglitazone and rosiglitazone. Xenobiotica. 2000 Jan;30(1):61-70.
5 Comparative Pharmacokinetics and Safety of Imrecoxib, a Novel Selective Cyclooxygenase-2 Inhibitor, in Elderly Healthy Subjects. Drug Des Devel Ther. 2022 Nov 8;16:3865-3876. doi: 10.2147/DDDT.S387508.
6 Acute pancreatitis in a patient treated with imatinib and gefitinib. J Oncol Pharm Pract. 2021 Jun;27(4):980-983. doi: 10.1177/1078155220949639.
7 Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
8 The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
9 Clinical pharmacokinetics of troglitazone Clin Pharmacokinet. 1999 Aug;37(2):91-104. doi: 10.2165/00003088-199937020-00001.
10 Intestinal motility and its disorders Scand J Urol Nephrol Suppl. 1992;142:18-21.

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