Identification
- Summary
Proguanil is a medication indicated for prophylaxis and treatment of Plasmodium falciparum malaria.
- Brand Names
- Malarone
- Generic Name
- Proguanil
- DrugBank Accession Number
- DB01131
- Background
Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase, which is involved in the reproduction of the parasite.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Proguanil (DB01131)
- Weight
- Average: 253.731
Monoisotopic: 253.109423244 - Chemical Formula
- C11H16ClN5
- Synonyms
- 1-(p-Chlorophenyl)-5-isopropylbiguanide
- Chlorguanide
- Chloroguanide
- Proguanil
- Proguanile
- Proguanilo
- Proguanilum
Pharmacology
- Indication
For the causal prevention and suppression of malaria caused by susceptible strains of P. falciparum and other species of Plasmodium found in some geographical areas of the world.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for prophylaxis of Malaria caused by plasmodium falciparum Combination Product in combination with: Atovaquone (DB01117) •••••••••••• Used in combination to treat Acute, uncomplicated malaria caused by plasmodium falciparum Combination Product in combination with: Atovaquone (DB01117) •••••••••••• - Contraindications & Blackbox Warnings
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Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against P. falciparum and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.
- Mechanism of action
Proguanil inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
Target Actions Organism ADihydrofolate reductase inhibitorHumans UBifunctional dihydrofolate reductase-thymidylate synthase inhibitorPlasmodium falciparum (isolate K1 / Thailand) - Absorption
Rapidly and well absorbed in humans following oral doses ranging from 50 to 500 mg.
- Volume of distribution
Not Available
- Protein binding
Approximately 75%
- Metabolism
Variably metabolized in the liver by cytochrome P450 isoenzymes to the active triazine metabolite, cycloguanil. This variable metabolism of proguanil may have profound clinical importance in poor metabolizers such as the Asian and African populations at risk for malaria infection. Prophylaxis with proguanil may not be effective in these persons because they may not achieve adequate therapeutic levels of the active compound, cycloguanil, even after multiple doses.
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- Route of elimination
Not Available
- Half-life
Approximately 20 hours
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*2 (A;A) A Allele, homozygote Effect Directly Studied Patients with this genotype have reduced metabolism of proguanil. Details Cytochrome P450 2C19 CYP2C19*3 (A;A) A Allele, homozygote Effect Directly Studied Patients with this genotype have reduced metabolism of proguanil. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor metabolizer, lower dose requirement Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Proguanil can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Proguanil. Acebutolol The metabolism of Acebutolol can be decreased when combined with Proguanil. Acenocoumarol Proguanil may increase the anticoagulant activities of Acenocoumarol. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Proguanil. - Food Interactions
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Proguanil hydrochloride R71Y86M0WT 637-32-1 SARMGXPVOFNNNG-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Paludrine
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Paludrine Tab 0.1gm Tablet 100 mg / tab Oral Ayerst Laboratories 1974-12-31 1997-08-15 Canada 
Paludrine Tab 100mg Tablet 100 mg Oral Wyeth Ayerst Canada Inc. 1996-10-25 2005-02-28 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Atovaquon/Proguanil-Hydrochlorid Glenmark 250 mg /100 mg Filmtabletten Proguanil hydrochloride (100 mg) + Atovaquone (250 mg) Tablet, film coated Oral Glenmark Arzneimittel Gmb H 2017-06-19 Not applicable Austria 
Atovaquon/Proguanilhydrochlorid STADA 250 mg/100 mg Filmtabletten Proguanil hydrochloride (100 mg) + Atovaquone (250 mg) Tablet, film coated Oral Stada Arzneimittel Gmb H 2012-08-22 Not applicable Austria Atovaquone and Proguanil HCl Proguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1) Tablet, film coated Oral Prasco Laboratories 2012-07-27 Not applicable US 
Atovaquone and Proguanil HCl Proguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1) Tablet, film coated Oral PD-Rx Pharmaceuticals, Inc. 2012-07-27 Not applicable US Atovaquone and Proguanil HCl Proguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1) Tablet, film coated Oral bryant ranch prepack 2012-07-27 Not applicable US
Categories
- ATC Codes
- P01BB01 — Proguanil
- P01BB — Biguanides
- P01B — ANTIMALARIALS
- P01 — ANTIPROTOZOALS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- P01BB — Biguanides
- P01B — ANTIMALARIALS
- P01 — ANTIPROTOZOALS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- Drug Categories
- Amidines
- Anti-Infective Agents
- Antimalarials
- Antimetabolites
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Biguanides
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Folic Acid Antagonists
- Guanidines
- Noxae
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1-arylbiguanides. These are organonitrogen compounds containing a biguanide that is N-arylsubstituted at only the 1-position.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Guanidines
- Direct Parent
- 1-arylbiguanides
- Alternative Parents
- Chlorobenzenes / Aryl chlorides / Carboximidamides / Organopnictogen compounds / Organochlorides / Imines / Hydrocarbon derivatives
- Substituents
- 1-arylbiguanide / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzenoid / Carboximidamide / Chlorobenzene / Halobenzene / Hydrocarbon derivative / Imine
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monochlorobenzenes, biguanides (CHEBI:8455)
- Affected organisms
- Plasmodium
Chemical Identifiers
- UNII
- S61K3P7B2V
- CAS number
- 500-92-5
- InChI Key
- SSOLNOMRVKKSON-UHFFFAOYSA-N
- 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)
- IUPAC Name
- 1-[N'-(4-chlorophenyl)carbamimidamido]-N-(propan-2-yl)methanimidamide
- SMILES
- CC(C)NC(=N)NC(=N)NC1=CC=C(Cl)C=C1
References
- Synthesis Reference
Dhananjay Govind Sathe, Harish Kashinath Mondkar, Tanaji Shamrao Jadhav, Nitin Nivrutti Hagavane, "Process of Preparation of Proguanil." U.S. Patent US20110263901, issued October 27, 2011.
US20110263901- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015263
- KEGG Compound
- C07631
- PubChem Compound
- 4923
- PubChem Substance
- 46506228
- ChemSpider
- 4754
- BindingDB
- 50227829
- 2382
- ChEBI
- 8455
- ChEMBL
- CHEMBL1377
- ZINC
- ZINC000095452610
- Therapeutic Targets Database
- DAP000634
- PharmGKB
- PA451124
- PDBe Ligand
- XEW
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Proguanil
- PDB Entries
- 8f4t
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- GlaxoSmithKline Inc.
- St Mary's Medical Park Pharmacy
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Tablet, film coated Oral 100 MG Tablet Oral Tablet Oral 100 mg / tab Tablet Oral 100 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 129 °C PhysProp water solubility 156 mg/L Not Available logP 2.53 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.116 mg/mL ALOGPS logP 2.29 ALOGPS logP 2.38 Chemaxon logS -3.3 ALOGPS pKa (Strongest Basic) 10.4 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 83.79 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 91.65 m3·mol-1 Chemaxon Polarizability 26.75 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9544 Blood Brain Barrier + 0.728 Caco-2 permeable + 0.5 P-glycoprotein substrate Non-substrate 0.7 P-glycoprotein inhibitor I Non-inhibitor 0.9482 P-glycoprotein inhibitor II Non-inhibitor 0.8511 Renal organic cation transporter Non-inhibitor 0.7381 CYP450 2C9 substrate Non-substrate 0.7646 CYP450 2D6 substrate Non-substrate 0.9115 CYP450 3A4 substrate Non-substrate 0.6085 CYP450 1A2 substrate Inhibitor 0.8751 CYP450 2C9 inhibitor Non-inhibitor 0.9591 CYP450 2D6 inhibitor Inhibitor 0.6507 CYP450 2C19 inhibitor Non-inhibitor 0.9405 CYP450 3A4 inhibitor Non-inhibitor 0.9109 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8774 Ames test Non AMES toxic 0.5887 Carcinogenicity Non-carcinogens 0.616 Biodegradation Not ready biodegradable 0.9939 Rat acute toxicity 2.6787 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9701 hERG inhibition (predictor II) Non-inhibitor 0.9265
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0006-9820000000-cb5312c89efbffe9e258 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0f7o-6920000000-9cc914f9810e8ef6a3c0 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-1190000000-e66f070862f9d55cf79d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0w2c-7920000000-eb0784ba4dcec84acd4d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0gbc-9200000000-c9d6c640944dc3839be1 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-9300000000-fd5c650b6b690e1e129d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0ikc-9300000000-82c14e50aa1e436a8c1d Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 143.2485782 predictedDarkChem Lite v0.1.0 [M-H]- 169.26653 predictedDeepCCS 1.0 (2019) [M+H]+ 144.8346782 predictedDarkChem Lite v0.1.0 [M+H]+ 171.62453 predictedDeepCCS 1.0 (2019) [M+Na]+ 143.5847782 predictedDarkChem Lite v0.1.0 [M+Na]+ 177.71767 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Nadph binding
- Specific Function
- Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA pre...
- Gene Name
- DHFR
- Uniprot ID
- P00374
- Uniprot Name
- Dihydrofolate reductase
- Molecular Weight
- 21452.61 Da
References
- Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Bjorkman A: Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis. 1999 Apr;179(4):974-9. [Article]
- Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, Zalis MG: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000 Sep-Oct;95(5):721-8. [Article]
- Tahar R, de Pecoulas PE, Basco LK, Chiadmi M, Mazabraud A: Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli. Mol Biochem Parasitol. 2001 Apr 6;113(2):241-9. [Article]
- Durand R, Jafari S, Bouchaud O, Ralaimazava P, Keundjian A, Le Bras J: Plasmodium falciparum: pfcrt and DHFR mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers. J Infect Dis. 2001 Dec 15;184(12):1633-4. [Article]
- Le Bras J, Durand R: The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam Clin Pharmacol. 2003 Apr;17(2):147-53. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Plasmodium falciparum (isolate K1 / Thailand)
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Thymidylate synthase activity
- Specific Function
- Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and f...
- Gene Name
- Not Available
- Uniprot ID
- P13922
- Uniprot Name
- Bifunctional dihydrofolate reductase-thymidylate synthase
- Molecular Weight
- 71816.775 Da
References
- Basco LK, Eldin de Pecoulas P, Wilson CM, Le Bras J, Mazabraud A: Point mutations in the dihydrofolate reductase-thymidylate synthase gene and pyrimethamine and cycloguanil resistance in Plasmodium falciparum. Mol Biochem Parasitol. 1995 Jan;69(1):135-8. doi: 10.1016/0166-6851(94)00207-4. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Lu AH, Shu Y, Huang SL, Wang W, Ou-Yang DS, Zhou HH: 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. [Article]
- Hoskins JM, Shenfield GM, Gross AS: Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population. Br J Clin Pharmacol. 1998 Nov;46(5):499-504. doi: 10.1046/j.1365-2125.1998.00807.x. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54