Halofantrine
Identification
- Summary
Halofantrine is an antimalarial used for the treatment of severe malaria.
- Generic Name
- Halofantrine
- DrugBank Accession Number
- DB01218
- Background
Halofantrine is an antimalarial. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It appears to inhibit polymerisation of heme molecules (by the parasite enzyme "heme polymerase"), resulting in the parasite being poisoned by its own waste. Halofantrine has been shown to preferentially block open and inactivated HERG channels leading to some degree of cardiotoxicity.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 500.424
Monoisotopic: 499.165654616 - Chemical Formula
- C26H30Cl2F3NO
- Synonyms
- Halofantrina
- Halofantrine
- Halofantrinum
- External IDs
- DL-WR-171669
Pharmacology
- Indication
For treatment of Severe malaria
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- Pharmacodynamics
Halofantrine is a synthetic antimalarial which acts as a blood schizonticide. It is effective against multi drug resistant (including mefloquine resistant) P. falciparum malaria.
- Mechanism of action
The mechanism of action of Halofantrine may be similar to that of chloroquine, quinine, and mefloquine; by forming toxic complexes with ferritoporphyrin IX that damage the membrane of the parasite.
Target Actions Organism AFe(II)-protoporphyrin IX antagonistPlasmodium falciparum APotassium voltage-gated channel subfamily H member 2 inhibitorHumans UPlasmepsin-2 inhibitorPlasmodium falciparum - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
60-70%;
- Metabolism
Hepatic
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
6-10 days
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Side effects incldue coughing noisy, rattling, troubled breathing, loss of appetite, aches and pain in joints, indigestion,and skin itching or rash.
- 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);">
- Not Available
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 softwareAbametapir The serum concentration of Halofantrine can be increased when it is combined with Abametapir. Abatacept The metabolism of Halofantrine can be increased when combined with Abatacept. Abiraterone The metabolism of Halofantrine can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Halofantrine can be decreased when combined with Acalabrutinib. Acebutolol The metabolism of Acebutolol can be decreased when combined with Halofantrine. - Food Interactions
- Take on an empty stomach. Food increases the bioavailability 6-fold, which may increase the risk of cardiotoxicity.
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 Halofantrine hydrochloride H77DL0Y630 36167-63-2 WANGFTDWOFGECH-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Halfan Tablet 250 mg/1 Oral GlaxoSmithKline 2006-09-20 2006-11-17 US Halfan - Tab 250mg Tablet 250 mg / tab Oral Smithkline Beecham Pharma Division Of Smithkline Beecham Inc 1996-07-16 1999-03-08 Canada
Categories
- ATC Codes
- P01BX01 — Halofantrine
- Drug Categories
- Agents that reduce seizure threshold
- Anti-Infective Agents
- Antimalarials
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strong)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Highest Risk QTc-Prolonging Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenanthrenes and derivatives
- Sub Class
- Not Available
- Direct Parent
- Phenanthrenes and derivatives
- Alternative Parents
- Chloronaphthalenes / Aralkylamines / Aryl chlorides / 1,3-aminoalcohols / Trialkylamines / Secondary alcohols / Organopnictogen compounds / Organofluorides / Organochlorides / Hydrocarbon derivatives show 2 more
- Substituents
- 1,3-aminoalcohol / Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aralkylamine / Aromatic alcohol / Aromatic homopolycyclic compound / Aryl chloride / Aryl halide show 15 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Plasmodium
Chemical Identifiers
- UNII
- Q2OS4303HZ
- CAS number
- 69756-53-2
- InChI Key
- FOHHNHSLJDZUGQ-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H30Cl2F3NO/c1-3-5-10-32(11-6-4-2)12-9-25(33)23-16-22-21(14-18(27)15-24(22)28)20-13-17(26(29,30)31)7-8-19(20)23/h7-8,13-16,25,33H,3-6,9-12H2,1-2H3
- IUPAC Name
- 3-(dibutylamino)-1-[1,3-dichloro-6-(trifluoromethyl)phenanthren-9-yl]propan-1-ol
- SMILES
- CCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015349
- KEGG Compound
- C07634
- PubChem Compound
- 37393
- PubChem Substance
- 46506753
- ChemSpider
- 34303
- BindingDB
- 79214
- 50749
- ChEBI
- 94392
- ChEMBL
- CHEMBL1107
- Therapeutic Targets Database
- DAP000953
- PharmGKB
- PA449839
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Halofantrine
- FDA label
- Download (84 KB)
- MSDS
- Download (27.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension Tablet Oral Tablet Oral 250 mg/1 Tablet Oral 250 mg / tab - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 8.9 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000111 mg/mL ALOGPS logP 7.34 ALOGPS logP 8.06 Chemaxon logS -6.7 ALOGPS pKa (Strongest Acidic) 14.47 Chemaxon pKa (Strongest Basic) 10.05 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 23.47 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 131.66 m3·mol-1 Chemaxon Polarizability 51.53 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.949 Caco-2 permeable + 0.6485 P-glycoprotein substrate Substrate 0.74 P-glycoprotein inhibitor I Inhibitor 0.6857 P-glycoprotein inhibitor II Inhibitor 0.6097 Renal organic cation transporter Non-inhibitor 0.5267 CYP450 2C9 substrate Non-substrate 0.8426 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.6218 CYP450 1A2 substrate Inhibitor 0.5513 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5252 Ames test Non AMES toxic 0.6185 Carcinogenicity Non-carcinogens 0.6485 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6809 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.732 hERG inhibition (predictor II) Inhibitor 0.9085
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 219.003749 predictedDarkChem Lite v0.1.0 [M-H]- 211.04655 predictedDeepCCS 1.0 (2019) [M+H]+ 219.703049 predictedDarkChem Lite v0.1.0 [M+H]+ 213.40453 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.460649 predictedDarkChem Lite v0.1.0 [M+Na]+ 220.20766 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Blauer G: Interaction of ferriprotoporphyrin IX with the antimalarials amodiaquine and halofantrine. Biochem Int. 1988 Oct;17(4):729-34. [Article]
- Egan TJ, Hempelmann E, Mavuso WW: Characterisation of synthetic beta-haematin and effects of the antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine on its formation. J Inorg Biochem. 1999 Jan-Feb;73(1-2):101-7. [Article]
- Famin O, Krugliak M, Ginsburg H: Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem Pharmacol. 1999 Jul 1;58(1):59-68. [Article]
- de Villiers KA, Marques HM, Egan TJ: The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials. J Inorg Biochem. 2008 Aug;102(8):1660-7. doi: 10.1016/j.jinorgbio.2008.04.001. Epub 2008 Apr 20. [Article]
- Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Tie H, Walker BD, Singleton CB, Valenzuela SM, Bursill JA, Wyse KR, Breit SN, Campbell TJ: Inhibition of HERG potassium channels by the antimalarial agent halofantrine. Br J Pharmacol. 2000 Aug;130(8):1967-75. [Article]
- Mbai M, Rajamani S, January CT: The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels. Cardiovasc Res. 2002 Sep;55(4):799-805. [Article]
- Kind
- Protein
- Organism
- Plasmodium falciparum
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Aspartic-type endopeptidase activity
- Specific Function
- Not Available
- Gene Name
- Not Available
- Uniprot ID
- P46925
- Uniprot Name
- Plasmepsin-2
- Molecular Weight
- 51489.41 Da
References
- Friedman R, Caflisch A: Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring. ChemMedChem. 2009 Aug;4(8):1317-26. doi: 10.1002/cmdc.200900078. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Halliday RC, Jones BC, Smith DA, Kitteringham NR, Park BK: An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4: studies with human liver microsomes and heterologous enzyme expression systems. Br J Clin Pharmacol. 1995 Oct;40(4):369-78. doi: 10.1111/j.1365-2125.1995.tb04559.x. [Article]
- Simooya OO, Sijumbil G, Lennard MS, Tucker GT: Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians. Br J Clin Pharmacol. 1998 Mar;45(3):315-7. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-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 performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Khoo SM, Porter JH, Edwards GA, Charman WN: Metabolism of halofantrine to its equipotent metabolite, desbutylhalofantrine, is decreased when orally administered with ketoconazole. J Pharm Sci. 1998 Dec;87(12):1538-41. doi: 10.1021/js980185w. [Article]
- Baune B, Flinois JP, Furlan V, Gimenez F, Taburet AM, Becquemont L, Farinotti R: Halofantrine metabolism in microsomes in man: major role of CYP 3A4 and CYP 3A5. J Pharm Pharmacol. 1999 Apr;51(4):419-26. [Article]
- Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Brentano C: Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther. 2002 Nov;72(5):514-23. doi: 10.1067/mcp.2002.128148b. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- 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
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Baune B, Flinois JP, Furlan V, Gimenez F, Taburet AM, Becquemont L, Farinotti R: Halofantrine metabolism in microsomes in man: major role of CYP 3A4 and CYP 3A5. J Pharm Pharmacol. 1999 Apr;51(4):419-26. [Article]
- 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
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Baune B, Flinois JP, Furlan V, Gimenez F, Taburet AM, Becquemont L, Farinotti R: Halofantrine metabolism in microsomes in man: major role of CYP 3A4 and CYP 3A5. J Pharm Pharmacol. 1999 Apr;51(4):419-26. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 07:02