artefenomel   Click here for help

GtoPdb Ligand ID: 9971

Synonyms: OZ439
Antimalarial Ligand
Compound class: Synthetic organic
Comment: Artefenomel is a synthetic ozonide (synthetic peroxide), a class of compound that retains the endoperoxide bridge of the artemisinin class of antimalarials but also contains the sterically bulky amantadine ring, which increases blood plasma stability [6].

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

artefenomel is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 5
Hydrogen bond donors 0
Rotatable bonds 5
Topological polar surface area 49.39
Molecular weight 469.28
XLogP 5.34
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O1CCN(CC1)CCOc1ccc(cc1)C1CCC2(CC1)OOC1(O2)C2CC3CC1CC(C2)C3
Isomeric SMILES O1CCN(CC1)CCOc1ccc(cc1)C1CCC2(CC1)OOC1(O2)C2CC3CC1CC(C2)C3
InChI InChI=1S/C28H39NO5/c1-3-26(31-14-11-29-9-12-30-13-10-29)4-2-22(1)23-5-7-27(8-6-23)32-28(34-33-27)24-16-20-15-21(18-24)19-25(28)17-20/h1-4,20-21,23-25H,5-19H2
InChI Key XLCNVWUKICLURR-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Artefenomel has a longer elimination half-life than other antimalarial endoperoxides and therefore has potential as a single-dose treatment when used with a partner drug. A Phase 2 clinical trial in which artefenomel will be used in combination with ferroquine (NCT02497612) has commenced recruitment. Results from a trial with piperaquine (NCT02083380, published in [4]) did not reach target efficacy as a single-dose treatment and a trial in combination with DSM265 (NCT02573857) has been terminated. Click here to view the full list of artefenomel trials registered with ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The ozonide class are thought to act on the Plasmodium proteostatic stress response: initially disrupting haemoglobin metabolism and following extended exposure, to reflect clinically-relevant treatment periods, additional parasite biochemical pathways were found to be perturbed [3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02083380 Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria. Phase 2/Phase 3 Interventional Medicines for Malaria Venture
NCT02497612 To Evaluate the Efficacy of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2 Interventional Sanofi
NCT02573857 A Study to Characterise the Antimalarial and Transmission Blocking Activity of a Single Dose of DSM265 or OZ439 in Healthy Subjects With Induced Blood Stage Plasmodium Falciparum or Plasmodium Vivax Infection Phase 1/Phase 2 Interventional Medicines for Malaria Venture
Pharmacokinetics Click here for help
Elimination
The estimated terminal half-life for elimination is 46 to 62 hours [5].