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

General Information of Drug (ID: DR1296)
Drug Name
Piperaquine
Synonyms
Piperaquine phosphate; Piperaquine tetraphosphate; Piperaquinoline; piperaquine; 1,3-Bis(4-(7-chloroquinolin-4-yl)piperazin-1-yl)propane; 4,4'-(propane-1,3-diyldipiperazine-4,1-diyl)bis(7-chloroquinoline); 4085-31-8; 7-chloro-4-[4-[3-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propyl]piperazin-1-yl]quinoline; A0HV2Q956Y; BRN 0905079; Quinoline, 4,4'-(1,3-propanediyldi-4,1-piperazinediyl)bis(7-chloro-; Quinoline, 4,4'-(1,3-propanediyldi-4,1-piperazinediyl)bis[7-chloro-; UNII-A0HV2Q956Y
Indication Malaria [ICD11: 1F40] Phase 4 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 535.5 Topological Polar Surface Area 38.7
Heavy Atom Count 37 Rotatable Bond Count 6
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
122262
PubChem SID
5950601 ; 10240000 ; 15334392 ; 29302678 ; 50043136 ; 57340047 ; 80274398 ; 92251569 ; 103134334 ; 103261382 ; 104415414 ; 117470297 ; 118048658 ; 118844030 ; 125350088 ; 129349514 ; 131314023 ; 135077962 ; 137123599 ; 138218944 ; 139440458 ; 143493527 ; 152035592 ; 152241247 ; 163653072 ; 164232665 ; 164824367 ; 174006179 ; 196105912 ; 198972196 ; 223701321 ; 224062913 ; 226500372 ; 249614087 ; 251912304 ; 251916614 ; 252411866
ChEBI ID
CHEBI:91231
CAS Number
4085-31-8
TTD Drug ID
D0P0SZ
Formula
C29H32Cl2N6
Canonical SMILES
C1CN(CCN1CCCN2CCN(CC2)C3=C4C=CC(=CC4=NC=C3)Cl)C5=C6C=CC(=CC6=NC=C5)Cl
InChI
1S/C29H32Cl2N6/c30-22-2-4-24-26(20-22)32-8-6-28(24)36-16-12-34(13-17-36)10-1-11-35-14-18-37(19-15-35)29-7-9-33-27-21-23(31)3-5-25(27)29/h2-9,20-21H,1,10-19H2
InChIKey
UCRHFBCYFMIWHC-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
Byproduct (piperaquine) DM004803
738389
Oxidation - N-dealkylation 1 [3] , [4]
M1 (piperaquine) DM004804
24873484
Oxidation - N-dealkylation 1 [3] , [4]
M2 (piperaquine) DM004800
71751683
Oxidation - N-oxidation 1 [3] , [4] , [5]
M3 (piperaquine) DM004807 N. A. Oxidation - Hydrolyzationn 1 [3]
M7 (piperaquine) DM004806 N. A. Oxidation - Hydrolyzationn 1 [3]
M5 (piperaquine) DM004801
146675103
Oxidation - N-oxidation 2 [3] , [4]
Piperaquine metabolite M4 DM004805 N. A. Oxidation - N-oxidation 2 [3] , [4]
Piperaquine metabolite M6 DM004802 N. A. Oxidation - N-oxidation 2 [3] , [4]
Piperaquine metabolite M6 DM004802 N. A. Unclear 2 [3] , [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005160 Piperaquine M2 (piperaquine) Oxidation - N-oxidation CYP3A4 [3], [4], [5]
MR005163 Piperaquine Byproduct (piperaquine) Oxidation - N-dealkylation Unclear [3], [4]
MR005165 Piperaquine M1 (piperaquine) Oxidation - N-dealkylation Unclear [3], [4]
MR005167 Piperaquine M7 (piperaquine) Oxidation - Hydrolyzationn Unclear [3]
MR005168 Piperaquine M3 (piperaquine) Oxidation - Hydrolyzationn Unclear [3]
MR005164 Byproduct (piperaquine) Piperaquine metabolite M6 Oxidation - N-oxidation Unclear [3], [4]
MR005166 M1 (piperaquine) Piperaquine metabolite M4 Oxidation - N-oxidation Unclear [3], [4]
MR005161 M2 (piperaquine) M5 (piperaquine) Oxidation - N-oxidation Unclear [3], [4]
MR005162 M2 (piperaquine) Piperaquine metabolite M6 Unclear Unclear [3], [4]
⏷ Show the Full List of 9 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3] , [4] , [5]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[6]
References
1 ClinicalTrials.gov (NCT02788864) Prevention of Malaria With Dihydroartemisinine + Piperaquine for Forest Rangers.
2 Eurartesim - European Medicines Agency
3 Characterization of human urinary metabolites of the antimalarial piperaquine
4 Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography-high-resolution mass spectrometry in combination with multiple data-mining tools in tandem
5 In vitro metabolism of piperaquine is primarily mediated by CYP3A4
6 Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.

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