Details of the Drug

General Information of Drug (ID: DMBL79I)

Drug Name
Proguanil
Synonyms
Bigumal; Chlorguanid; Chlorguanide; Chloriguane; Chloroguanide; Paludrin; Proguanile; Proguanilum; Proguanile [DCIT]; Diguanyl (hydrochloride); Drinupal (hydrochloride); Paludrine (TN); Paludrine (hydrochloride); Palusil (hydrochloride); Proguanil [INN:BAN]; Proguanilum [INN-Latin]; RP-3359; Tirian (hydrochloride); M-4888 (hydrochloride); SN-12837 (hydrochloride); N1-p-Chlorophenyl-N5-isopropylbiguanide; N-(4-Chlorophenyl)-N'-(1-methylethyl)imidodicarbonimidic diamide; N-(4-Chlorophenyl)-N'-(isopropyl)-imidodicarbonimidic diamide; N-(4-chlorophenyl)-N'-(propan-2-yl)imidodicarbonimidic diamide; (1E)-1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine; 1-(p-Chlorophenyl)-5-isopropylbiguanide; 1-Isopropyl-5-(4-chlorophenyl)biguanide
Indication
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [1]
Therapeutic Class
Antimalarials
Affected Organisms
Plasmodium
ATC Code
P01BB01: Proguanil
P01BB: Biguanides
P01B: ANTIMALARIALS
P01: ANTIPROTOZOALS
P: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 253.73
Logarithm of the Partition Coefficient (xlogp) 1.5
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 1
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability
60% of drug becomes completely available to its intended biological destination(s) [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 20 hours [4]
Metabolism
The drug is metabolized via the liver []
Water Solubility
The ability of drug to dissolve in water is measured as 9.09 mg/mL [2]
Chemical Identifiers
Formula
C11H16ClN5
IUPAC Name
(1E)-1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine
Canonical SMILES
CC(C)N=C(N)/N=C(\\N)/NC1=CC=C(C=C1)Cl
InChI
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
Cross-matching ID
PubChem CID
6178111
ChEBI ID
CHEMBL1377
CAS Number
500-92-5
UNII
S61K3P7B2V
DrugBank ID
DB01131
TTD ID
D0P8RS
INTEDE ID
DR1347
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [8]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Malaria
ICD Disease Classification 1F40-1F45
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Polypeptide deformylase (PDF) DTT PDF 8.87E-16 -0.54 -0.86
Cytochrome P450 2E1 (CYP2E1) DME CYP2E1 1.94E-06 7.00E-02 4.44E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.09E-03 2.84E-02 1.20E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 6.34E-01 4.42E-03 2.22E-02
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 5.63E-01 -9.82E-03 -4.80E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 7.29E-03 -3.47E-02 -1.80E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Proguanil (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Sodium bicarbonate DMMU6BJ Moderate Decreased absorption of Proguanil due to adsorption of Sodium bicarbonate. Acidosis [5C73] [10]
Arn-509 DMT81LZ Moderate Increased metabolism of Proguanil caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [10]
Cenobamate DM8KLU9 Moderate Decreased metabolism of Proguanil caused by Cenobamate mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [11]
Brivaracetam DMSEPK8 Minor Decreased metabolism of Proguanil caused by Brivaracetam mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [10]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Proguanil caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [10]
Enzalutamide DMGL19D Moderate Increased metabolism of Proguanil caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [12]
Armodafinil DMGB035 Moderate Decreased metabolism of Proguanil caused by Armodafinil mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [13]
⏷ Show the Full List of 7 DDI Information of This Drug

References

1 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
2 BDDCS applied to over 900 drugs
3 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
6 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.
7 Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67.
8 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9 Polymorphic oxidative metabolism of proguanil in a Nigerian population. Eur J Clin Pharmacol. 2002 Nov;58(8):543-5.
10 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
11 Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
12 Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
13 Cerner Multum, Inc. "Australian Product Information.".