MK-7602 acts as a dual inhibitor of plasmepsins IX and X in P. falciparum

MK-7602, a clinical candidate, acts as a dual sub-nanomolar inhibitor of plasmepsins IX and X in multiple Plasmodium species. It exhibits favourable pharmacokinetic properties and a promising safety profile. MK-7602 demonstrates activity against liver and blood life-cycle stages of the parasite and blocks transmission to mosquitoes. Importantly, it shows a high barrier to resistance development and lacks cross-resistance with P. falciparum strains resistant to other antimalarials. MK-7602 effectively inhibits both wild-type parasites and those with increased plasmepsin expression, highlighting its potential to overcome existing resistance mechanisms.