MK-7602 is a potent multi-stage dual-targeting antimalarial compound, is a dual inhibitor of plasmepsins IX and X with Ki of 0.132 nM and 0.683 nM for PfPMX and PfPMIX respectively, inhibits inhibit asexual growth of P. falciparum with EC50 of 0.4 nM.
MK-7602 is a potent dual inhibitor of the aspartic protease activity of both P. falciparum PMIX (PfPMIX) (Ki 0.68 nM) and PMX (PfPMX) (Ki 0.13 nM) and it also inhibited PMX from both P. vivax (PvPMX) (Ki 0.03 nM) and P. knowlesi (PkPMX) (Ki 0.09 nM).
MK-7602 has strong selectivity for dual inhibition of PfPMIX and PfPMX compared to other aspartic proteases including P. vivax plasmepsin V (PvPMV) (174,374-fold, PMV/PMX) and the human proteases BACE1 (>43,426-fold, BACE1/PMX), cathepsin D (CatD) (21,443-fold, CatD/PMX) and renin (4250-fold, renin/PMX).
MK-7602 displays >4000-fold selectivity versus these human proteases.
MK-7602 inhibits P. falciparum development in the blood stage, inhibits P. falciparum blood stage parasite growth.
MK-7602 is effective against blood stage P. berghei mouse models of malaria.