tafenoquine   Click here for help

GtoPdb Ligand ID: 9722

Synonyms: Arakoda® | etaquine | Krintafel® | WR238605
Approved drug Antimalarial Ligand
tafenoquine is an approved drug (FDA (2018))
Compound class: Synthetic organic
Comment: Tafenoquine is an 8-aminoquinoline derivative that has potent antimalarial activity and is a synthetic analogue of primaquine.
The INN record for tafenoquine indicates that it is a racemic mixture. We show the chemical structure without stereochemistry to represent the mixture. The non-isomeric structure is also represented in the PubChem and ChEMBL entries listed in the links table below, while the two enantiomers forming the racemate are represented by PubChem CID 76969187 and PubChem CID 76969188.

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 3
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 78.63
Molecular weight 463.21
XLogP 5.3
No. Lipinski's rules broken 1
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 NCCCC(Nc1cc(OC)c(c2c1nc(OC)cc2C)Oc1cccc(c1)C(F)(F)F)C
Isomeric SMILES NCCCC(Nc1cc(OC)c(c2c1nc(OC)cc2C)Oc1cccc(c1)C(F)(F)F)C
InChI InChI=1S/C24H28F3N3O3/c1-14-11-20(32-4)30-22-18(29-15(2)7-6-10-28)13-19(31-3)23(21(14)22)33-17-9-5-8-16(12-17)24(25,26)27/h5,8-9,11-13,15,29H,6-7,10,28H2,1-4H3
InChI Key LBHLFPGPEGDCJG-UHFFFAOYSA-N
Bioactivity Comments
The interaction table below provides data from an evaluation of the antimalarial (asexual blood stage) activity of tafenoquine, using a panel of P. falciparum strains and field isolates, with the results for strains W2 and D6 provided in the table (average IC50 for panel = 436nM).
Whole organism assay data
Key to terms and symbols Click on species/strain names for details Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA PfW2

Plasmodium falciparum W2

P. falciparum strain W2 (PfW2) was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfW2 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and susceptible to mefloquine.
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 Parasite growth inhibition assay - - 6.7 pIC50 - 6
⤷ pIC50 6.7 (IC50 2.17x10-7 M) [3H]-hypoxanthine incorporation [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfD6

Plasmodium falciparum D6

P. falciparum strain D6 (PfD6) was collected in Sierra Leone.
PfD6 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is generally considered drug sensitive with minor mefloquine resistance.
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 Parasite growth inhibition assay - - 5.8 pIC50 - 6
⤷ pIC50 5.8 (IC50 1.47x10-6 M) [3H]-hypoxanthine incorporation [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pc

Plasmodium cynomolgi

P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite).
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 Parasite liver stage assay - - - - - 7
⤷ P. cynomolgi infected primary rhesus hepatocyte assay, 70-90% inhibition of hypnozoites at 10µM [7]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
P. cynomolgi infected primary rhesus hepatocyte assay, >90% inhibition of schizonts at 10µM [7]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)