Manogepix

Manogepix (E1210) is a first-in-class, broad-spectrum and orally active antifungal. Manogepix has a mechanism of action-inhibition of fungal glycosylphosphatidylinositol (GPI) biosynthesis^[1][2]. IC50 & Target:Fungal^[1][2] In Vitro:Manogepix inhibits the inositol acylation activity of C. albicans Gwt1p and A. fumigatus Gwt1p with IC₅₀s of 0.3 to 0.6 μM but has no inhibitory activity against human Pig-Wp even at concentrations as high as 100 μM. To confirm the inhibition of fungal glycosylphosphatidylinositol (GPI) biosynthesis, expression of ALS1 protein, a GPI-anchored protein, on the surfaces of C. albicans cells treated with Manogepix is studied and shown to be significantly lower than that on untreated cells. Manogepix inhibits germ tube formation, adherence to polystyrene surfaces, and biofilm formation of C. albicans at concentrations above its MIC^[1]. In Vivo:Manogepix (2.5 mg/kg, 5 mg/kg and 10 mg/kg; oral administration; twice daily; for 3 days; specific-pathogen-free female ICR mice) treatment reduces the number of viable C. albicans cells in the oral cavity in a dose-dependent manner^[2].