halofantrine   Click here for help

GtoPdb Ligand ID: 10019

Synonyms: Halfan® | WR-171669
Approved drug Antimalarial Ligand
halofantrine is an approved drug (FDA (1992))
Compound class: Synthetic organic
Comment: Halofantrine is a phenanthrene containing compound and belongs to the aryl amino alcohols, a chemical class of antimalarial drugs that includes quinine, mefloquine and lumefantrine.
The INN record specifies that halofantrine is a racemic mixture of stereoisomers. We show the structure without specified stereochemistry to represent the mixture.
The marketed formulation contains halofantrine hydrochloride (PubChem CID 37392).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 23.47
Molecular weight 499.17
XLogP 8.93
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCCCN(CCC(c1cc2c(Cl)cc(cc2c2c1ccc(c2)C(F)(F)F)Cl)O)CCCC
Isomeric SMILES CCCCN(CCC(c1cc2c(Cl)cc(cc2c2c1ccc(c2)C(F)(F)F)Cl)O)CCCC
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
InChI Key FOHHNHSLJDZUGQ-UHFFFAOYSA-N
Guide to Malaria Pharmacology Comments
Halofantrine was developed by the Walter Reed Army Institute of Research and was a key compound identified during a antimalarial drug discovery programme that ran from 1963 until 1976 [2]. The licensed drug was used in the treatment of both P. falciparum and P. vivax malaria but this has declined significantly due to potentially lethal cardiotoxic side effects and variable pharmacokinetic properties. It is not recommended for prophylactic use.

Potential Target/Mechanism Of Action: As the precise mechanism of action of halofantrine is not yet known, we do not have a molecular target for this compound. There is some evidence that suggests that halofantrine inhibits the haem detoxification pathway in the parasite, and that this action causes lethal haem toxicity [1,3].