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

General Information of Drug (ID: DR1295)
Drug Name
Pioglitazone hydrochloride
Synonyms
Pioglitazona; Pioglitazona [INN-Spanish]; Pioglitazone; Pioglitazone (Actos); Pioglitazone [BAN:INN]; Pioglitazone [INN:BAN]; Pioglitazonum; Pioglitazonum [INN-Latin]; Pioditazone hydrochloride; Pioglitazone (hydrochloride); Pioglitazone HCl; U-72107A; U-72107E; pioglitazone hydrochloride; (+-)-5-(p-(2-(5-Ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione monohydrochloride; 112529-15-4; 5-(4-(2-(5-Ethylpyridin-2-yl)ethoxy)benzyl)thiazolidine-2,4-dione hydrochloride; AD 4833; C19H21ClN2O3S; DSSTox_CID_24203; DSSTox_GSID_44203; DSSTox_RID_80116; MFCD04975446; NCGC00095131-01; [5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione hydrochloride; U 72107; Zactos; 105355-27-9; 111025-46-8; 5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)thiazolidine-2,4-dione; 5-[4-[2-(5-ETHYL-2-PYRIDYL)ETHOXY]BENZYL]-2,4-THIAZOLIDINEDIONE; 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione; AD-4833; Actos; C19H20N2O3S; CHEBI:8228; HSDB 7322; Duetact; Glustin
Indication Diabetes mellitus [ICD11: 5A10] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 392.9 Topological Polar Surface Area 93.6
Heavy Atom Count 26 Rotatable Bond Count 7
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
60560
ChEBI ID
CHEBI:8229
CAS Number
112529-15-4
TTD Drug ID
D03OFF
Formula
C19H21ClN2O3S
Canonical SMILES
CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3.Cl
InChI
1S/C19H20N2O3S.ClH/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17;/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23);1H
InChIKey
GHUUBYQTCDQWRA-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
Pioglitazone metabolite M-I DM002853
10198397
Oxidation - O-Dealkylation 1 [4] , [6]
Pioglitazone metabolite M-II DM002854
9864268
Oxidation - Oxidation 1 [4] , [6]
Pioglitazone metabolite M-IV DM002859
4147757
Oxidation - Oxidation 1 [4] , [6]
Pioglitazone metabolite M-V DM002858
10068721
Oxidation - Oxidation 1 [4] , [6]
Pioglitazone metabolite M-VI DM002857
45038858
Oxidation - Oxidation 1 [4]
Pioglitazone metabolite M-VII DM002861
71434033
Oxidation - Hydroxylation 1 [7]
Mitoglitazone DM002856
10429242
Oxidation - Oxidation 2 [4] , [6]
Pioglitazone metabolite M-III DM002860
5201446
Oxidation - Oxidation 2 [4] , [6]
Pioglitazone metabolite M-VI DM002857
45038858
Unclear 2 [4] , [6]
Pioglitazone metabolite M-XI DM002855
162625100
Oxidation - Oxidation 2 [4] , [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002050 Pioglitazone hydrochloride Pioglitazone metabolite M-I Oxidation - O-Dealkylation Unclear [4], [6]
MR002051 Pioglitazone hydrochloride Pioglitazone metabolite M-II Oxidation - Oxidation CYP3A4 ... [4], [6]
MR002052 Pioglitazone hydrochloride Pioglitazone metabolite M-VI Oxidation - Oxidation CYP3A4 ... [4]
MR002053 Pioglitazone hydrochloride Pioglitazone metabolite M-V Oxidation - Oxidation CYP3A4 ... [4], [6]
MR002054 Pioglitazone hydrochloride Pioglitazone metabolite M-IV Oxidation - Oxidation CYP3A4 ... [4], [6]
MR002055 Pioglitazone hydrochloride Pioglitazone metabolite M-VII Oxidation - Hydroxylation Unclear [7]
MR002045 Pioglitazone metabolite M-II Pioglitazone metabolite M-XI Oxidation - Oxidation CYP3A4 ... [4], [6]
MR002046 Pioglitazone metabolite M-II Mitoglitazone Oxidation - Oxidation Unclear [4], [6]
MR002048 Pioglitazone metabolite M-IV Pioglitazone metabolite M-XI Oxidation - Oxidation CYP3A4 ... [4], [6]
MR002049 Pioglitazone metabolite M-IV Pioglitazone metabolite M-III Oxidation - Oxidation Unclear [4], [6]
MR002047 Pioglitazone metabolite M-V Pioglitazone metabolite M-VI Unclear Unclear [4], [6]
⏷ Show the Full List of 11 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 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[5]
References
1 Pioglitazone Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 The role of human CYP2C8 and CYP2C9 variants in pioglitazone metabolism in vitro. Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):374-9.
3 Current clinical evidence on pioglitazone pharmacogenomics. Front Pharmacol. 2013 Nov 26;4:147.
4 Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51.
5 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.
6 Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction J Pharm Biomed Anal. 1996 Feb;14(4):465-73. doi: 10.1016/0731-7085(95)01665-1.
7 Identification of novel metabolites of pioglitazone in rat and dog Xenobiotica. 2003 May;33(5):499-509. doi: 10.1080/0049825031000085951.

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