ArticleProceedings of the National Academy of Sciences of the United States of America2011
Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed.
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- Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.The Lancet. Infectious diseases · 2016Trial
- First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials.British journal of clinical pharmacology · 2013Trial
- Synthesis, Structure, and Antileishmanial Activity of Novel 1,2,4-Trioxolanes, 1,2,4,5-Tetraoxanes and Their Respective Deoxygenated Controls.ChemMedChem · 2026Article
- Antischistosomal Ozonide Glycine Ethyl Esters.ACS medicinal chemistry letters · 2026Article
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- A Stereospecific Synthesis and In Vitro Anti-Influenza H1N1 Properties of Lithocholic Acid-BasedMolecules (Basel, Switzerland) · 2025Article
- Structure-Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity.Journal of medicinal chemistry · 2025Article
- Three decades of selective product formationRSC advances · 2025Review
- Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.Science advances · 2025Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Natural products as transmission-blocking agents against malaria: a comprehensive review of bioactive compounds and their therapeutic potential.Malaria journal · 2025Review
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol.Malaria journal · 2024Article
- Addressing the Intracellular Vestibule of the Plasmodial Lactate Transporter PfFNT by p-Substituted Inhibitors Amplifies In Vitro Activity.Journal of medicinal chemistry · 2024Article
- Synthesis and In Vivo Profiling of Desymmetrized Antimalarial Trioxolanes with Diverse Carbamate Side Chains.ACS medicinal chemistry letters · 2024Article
- Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges.Journal of epidemiology and global health · 2024Review
108 more citing papers are in PubMed but not listed here.
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27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC(50) values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei-infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death.
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