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atovaquone + proguanil + amodiaquine
- Development stage
- Unknown
- Lead developer
- Medicines for Malaria Venture
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Atovaquone-proguanil + amodiaquine (ATV-PG + AQ) is an investigational small molecule combination regimen developed by Medicines for Malaria Venture (MMV). It was designed as a potential replacement for the sulfadoxine-pyrimethamine plus amodiaquine regimen used for seasonal malaria chemoprevention (SMC) in African children. The combination consists of atovaquone, which inhibits mitochondrial electron transport by targeting the cytochrome bc1 complex; proguanil, which acts as a dihydrofolate reductase inhibitor; and amodiaquine, a 4-aminoquinoline that interferes with heme detoxification in the parasite. A Phase 1 study (NCT04002687) conducted in healthy adult volunteers of sub-Saharan African origin evaluated the safety, tolerability, and pharmacokinetics of the regimen. However, the trial identified an unanticipated CNS safety signal involving transient extrapyramidal symptoms in participants receiving the combination, which has raised significant concerns regarding its further development for seasonal malaria chemoprevention.
- Brand names
- MalaroneMalanil
- Other names
- atovaquone-proguanil + amodiaquine
02
Targets
HemeDHFR-TS (Bifunctional dihydrofolate reductase-thymidylate synthase)bc1 complex (Cytochrome bc1 complex (plasmodium))
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