Figure 2.

Notable frontline antimalarials with targets throughout the lifecycle.

Selected antimalarials with activity against different stages of the parasite lifecycle. "Me" denotes methyl groups. KAE609 is a PfATP4 inhibitor which shows fast parasite clearance and transmission-blocking potential and is currently undergoing phase II clinical trials. Decoquinate is a dual-stage antimalarial (ABS and liver) with activity against the parasite mitochondrial bc1 complex. Primaquine and tafenoquine are the only liver-stage targeted compounds with the ability to kill hypnozoites in use despite their side effects. KAI407 is a hypnozoitocidal compound identified using P. cynomolgi sporozoites and primary monkey hepatocytes that targets the ABS and developing liver stage parasites as well. TM2-115 is a putative histone methyltransferase inhibitor with activity against both asexual and sexual stages, and the ability to induce dormant liver stages to resume their maturation. Methylene blue is a classical antimalarial showing transmission-blocking activity regardless of assay read-out and can thus be used as positive control in screening campaigns. DD01035881 is a male-gamete formation inhibitor identified from the GHCDL screen. KAF156 is a drug candidate with activity against ABS, liver and sexual stages, which was developed through the optimisation of a hit identified in one of the first liver stage screens. DDD107498 is a eEF2 inhibitor with activity across all parasite stages. Primaquine, Tafenoquine and DDD1035881 are used as racemates.