NEU-4438

NEU-4438 is an antimalarial agent. NEU-4438 inhibits DNA synthesis, reduces AMPK-γ, and increases Clathrin heavy chain. NEU-4438 exhibits antiparasitic activity against Trypanosoma brucei. NEU-4438 reduces trypanosome tissue burden in a chronic HAT mouse model^[1]. In Vitro:NEU-4438 (serial dilutions; 6 h, then 48 h in drug-free medium) induces delayed trypanocidality in bloodstream Trypanosoma brucei brucei Lister427 cells, with a DC₅₀ of 334 nM after 6 h treatment followed by 48 h in drug-free medium^[1].
NEU-4438 (150-1013 nM; 6 h) dose-dependently reduces AMPK-γ protein levels and increases clathrin heavy chain levels in bloodstream Trypanosoma brucei cells expressing Myc-tagged versions of these proteins, with maximal effects at 1013 nM (DC₉₀) after 6 h treatment^[1].
NEU-4438 (150 nM; 6 h, then 1 h EdU labeling) inhibits nuclear DNA synthesis in bloodstream Trypanosoma brucei brucei Lister427 cells, as shown by a reduction in EdU-positive cells and decreased nuclear EdU signal intensity^[1]. In Vivo:NEU-4438 (120-150 mg/kg; daily; days 1-7 post-infection) achieves greater than 100-fold reduction in median trypanosome tissue load in a mouse model of chronic HAT by day 7 post-infection, though the dosing regimen does not produce a cure by day 14^[1].