Antimalarial efficacy of MMV390048 has potential as new anti-malarial drug

Professor Kelly Chibale (Department of Chemistry, UCT, and IDM Member) and colleagues recently described and confirmed the discovery and preclinical evaluation of the novel antimalarial, MMV390048, showing potential as a new anti-malarial drug, contributing to global malaria eradication efforts.

Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Tanya Paquet et al. Science Translational Medicine (2017) 9(387): eaad9735. DOI: 10.1126/scitranslmed.aad9735

Paquet et al. screened a small-molecule library against the human malaria parasite, Plasmodium falciparum, and identified the 2-aminopyridine chemical class with potent activity. The optimized compound from this class, MMV390048, was active against multiple parasite life cycle stages, in both the mammalian host and the mosquito vector, and also killed drug-resistant parasites. MMV390048 killed the malaria parasite by blocking the parasite’s phosphatidylinositol 4-kinase (PI4K) and was able to protect monkeys from malaria infection. The ability of MMV390048 to block all life cycle stages of the malaria parasite suggests that this compound should be further developed and may contribute to malaria control and eradication as part of a single-dose combination treatment.