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.
2D Structure
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Physico-chemical Properties
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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
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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
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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
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
The estimated terminal half-life for elimination is 46 to 62 hours [5].