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

General Information of Drug (ID: DR1347)
Drug Name
Proguanil
Prodrug Info Proguanil is the prodrug of Cycloguanil
Synonyms
Paludrin; Paludrine; Proguanil [INN:BAN]; Proguanile; Proguanile [DCIT]; Proguanilum; Proguanilum [INN-Latin]; S61K3P7B2V; Bigumal; Chlorguanid; Chlorguanide; Chloriguane; Chloroguanide; proguanil; 1-(p-Chlorophenyl)-5-isopropylbiguanide; 1-Isopropyl-5-(4-chlorophenyl)biguanide; 500-92-5; BIGUANIDE, 1-(p-CHLOROPHENYL)-5-ISOPROPYL-; BRN 2811599; C11H16ClN5; CHEBI:8455; EINECS 207-915-6; Imidodicarbonimidic diamide, N-(4-chlorophenyl)-N'-(1-methylethyl)-; N1-p-Chlorophenyl-N5-isopropylbiguanide; UNII-S61K3P7B2V
Indication Malaria [ICD11: 1F40] Phase 4 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 253.73 Topological Polar Surface Area 88.8
Heavy Atom Count 17 Rotatable Bond Count 4
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 1
Cross-matching ID
PubChem CID
6178111
PubChem SID
9833 ; 603149 ; 7980396 ; 11112433 ; 11341938 ; 11362121 ; 11364482 ; 11367044 ; 11369606 ; 11372736 ; 11374343 ; 11377768 ; 11467027 ; 11468147 ; 11484765 ; 11486724 ; 11487523 ; 11488951 ; 11491474 ; 11492437 ; 11495402 ; 14823534 ; 47736673 ; 47885583 ; 47959951 ; 48035321 ; 48035322 ; 48185162 ; 48415754 ; 49698968 ; 49893807 ; 50100438 ; 50100439 ; 57309709 ; 57365545 ; 80043130 ; 85788592 ; 87246413 ; 93166734 ; 96025114 ; 103462237 ; 114370477 ; 134978163 ; 137004047 ; 137040200 ; 137131382 ; 160964465 ; 162188072 ; 175267378 ; 179039118
ChEBI ID
CHEBI:8455
CAS Number
500-92-5
TTD Drug ID
D0P8RS
Formula
C11H16ClN5
Canonical SMILES
CC(C)N=C(N)N=C(N)NC1=CC=C(C=C1)Cl
InChI
1S/C11H16ClN5/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)
InChIKey
SSOLNOMRVKKSON-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
4-Chlorophenylbiguanide DM004824
19933
Oxidation - N-dealkylation 1 [6] , [7]
Cycloguanil DM004823
9049
Other reaction - Cyclisation 1 [4] , [6] , [7]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005189 Proguanil Cycloguanil Other reaction - Cyclisation CYP3A4 ... [4], [6], [7]
MR005190 Proguanil 4-Chlorophenylbiguanide Oxidation - N-dealkylation CYP2C19 [6], [7]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[5]
References
1 ClinicalTrials.gov (NCT02297477) The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia.
2 Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67.
3 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
4 In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52.
5 Polymorphic oxidative metabolism of proguanil in a Nigerian population. Eur J Clin Pharmacol. 2002 Nov;58(8):543-5.
6 Sensitive method for the quantitative determination of proguanil and its metabolites in rat blood and plasma by liquid chromatography-mass spectrometry
7 Single dose pharmacokinetics of proguanil and its metabolites in pregnancy

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