mmv390048

MMV390048 is an antimalarial agent and is a representative of a new chemical class of Plasmodium PI4K inhibitor (Kdapp=0.3 μM). MMV390048 binds to the ATP binding site of Plasmodium PI4K and does not bind to other P. falciparum and human kinases apart from human PIP4K2C, thus alleviating potential kinase-mediated safety concerns.

MMV666810, a 2-aminopyrazine analogue of MMV390048, exhibits potent antiplasmodial activity against asexual parasites with an IC50 value of 5.94 nM. It demonstrates enhanced efficacy against late-stage gametocytes with a 3.3-fold higher selectivity relative to early stages (early-stage gametocyte: IC50 603 ± 88 nM; late-stage gametocyte: IC50 179 ± 8 nM).