MMV688533 is a potent antimalarial compound that displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials, MMV688533 is highly potent against multiple P. falciparum strains with IC50 values in low nanomolar range (P. falciparum 3D7, IC50=1.9 nM).
MMV688533 also showed excellent ex vivo activity against asexual blood-stage parasites from fresh P. falciparum isolates (median IC50=1.3 nM, range=0.02 to 6.3 nM).
MMV688533 remained potent in ex vivo assays against both P. falciparum and P. vivax with IC50 of 18.9 and 12.0 nM respectively.
MMV688533 displayed fast and potent in vivo efficacy and favorable in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic properties.
MMV688533 antiplasmodial activity is unrelated to existing antimalarials and selects for low-grade resistance mediated in part by mutations in PfACG1 and PfEHD.