E1210 (Synonyms: APX001A)

E1210 is a first-in-class, broad-spectrum and orally active antifungal. E1210 has a mechanism of action-inhibition of fungal glycosylphosphatidylinositol (GPI) biosynthesis[1][2].

E1210 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 E1210 is studied and shown to be significantly lower than that on untreated cells. E1210 inhibits germ tube formation, adherence to polystyrene surfaces, and biofilm formation of C. albicans at concentrations above its MIC[1].

E1210 (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]. Animal Model: Specific-pathogen-free female ICR mice (5 weeks; ~25 g) with C. albicans[2]

[1]. Watanabe NA, et al. E1210, a new broad-spectrum antifungal, suppresses Candida albicans hyphal growth through inhibition of glycosylphosphatidylinositol biosynthesis. Antimicrob Agents Chemother. 2012 Feb;56(2):960-71. [2]. Hata K, et al. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob Agents Chemother. 2011 Oct;55(10):4543-51.