DDD9309

DDD9309 is an optimized small-molecule inhibitor of *Plasmodium falciparum* acetyl-CoA synthetase (PfAcAS), developed by the University of Dundee in collaboration with the Malaria Drug Accelerator (MalDA) consortium. As an optimized analogue of the PfAcAS inhibitor MMV019721, DDD9309 exhibits improved biochemical and cellular potency, with an enzyme IC50 of 16 nM and a 3D7 EC50 of 40 nM. The compound targets acetyl-CoA biosynthesis, disrupting the development of both early and late-stage gametocytes and reducing histone acetylation. This epigenetic modulation impairs gametocytogenesis and blocks transmission of the malaria parasite through its mosquito stages, making DDD9309 a promising candidate for multi-stage malaria treatment and transmission prevention.