manogepix

Manogepix (APX001A) is a first-in-class small molecule antifungal agent and the active moiety of the prodrug fosmanogepix (APX001). It exhibits broad-spectrum activity against major human-pathogenic fungi, including multidrug-resistant Candida auris, Candida spp., Aspergillus spp., Cryptococcus, Scedosporium, Fusarium, and members of the Mucorales order. Manogepix acts by inhibiting the highly conserved fungal enzyme Glycosylphosphatidylinositol-anchored wall transfer protein 1 (Gwt1), which is essential for GPI-anchor biosynthesis in fungal cell walls. Inhibition of Gwt1 disrupts cell wall integrity, impairs biofilm formation and filamentation, enhances immunogenicity by unmasking β-glucan, and leads to severe growth defects in fungi. The closest mammalian ortholog to Gwt1 is PIG-W; however, it is not inhibited by manogepix. Manogepix has demonstrated potent activity against azole- and echinocandin-resistant strains with no observed cross-resistance with other antifungal classes. The drug is being developed primarily for invasive candidiasis/candidemia (including C. auris) and invasive aspergillosis[1][3][4][5][6].

Other names

manogepix