MMV693183

MMV693183 is an orally active inhibitor of Plasmodium falciparum acetyl-CoA synthetase (AcAS), with an IC₅₀ of 300 nM against Plasmodium falciparum. MMV693183 exhibits potent inhibitory activity against clinical isolates of malaria parasites, including Artemisinin (HY-B0094)-resistant strains. MMV693183 is metabolized in vivo into the active antimetabolite CoA-MMV693183, which exerts effects of killing asexual blood-stage parasites and blocking transmission to Anopheles mosquitoes by binding to and inhibiting the function of acetyl-CoA synthetase, thereby reducing the levels of acetyl-CoA and 4'-phosphopantetheine. In humanized mouse models, MMV693183 shows favorable in vivo efficacy, drug-like properties, and no significant cytotoxicity or off-target activity against human cells. MMV693183 is widely used in malaria-related research as a parasiticide and metabolic disruptor^[1].