The Investigational Agent E1210 Is Effective in Treatment of Experimental Invasive Candidiasis Caused by Resistant Candida albicans

Abstract

cThe in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandinresistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistant C. albicans infections.

APX001 Pharmacokinetic/Pharmacodynamic Target Determination against Aspergillus fumigatus in an In Vivo Model of Invasive Pulmonary Aspergillosis

“…This leads to pleotropic effects, including compromised cell wall integrity, and a reduction in fungal virulence attributes, including biofilm and germ tube formation, all of which ultimately contribute to severe fungal growth defects. APX001A/APX001 has potent broad in vitro and in vivo activity against major fungal pathogens, including Candida, Cryptococcus, Aspergillus, Scedosporium, and Fusarium strains, regardless of their azole resistance and echinocandin resistance, which is consistent with the distinct mechanism of action (16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

The antifungal pipeline: a reality check

“…Furthermore, APX001 has excellent, broad-spectrum potency with antifungal activity in vitro against Candida spp. and Aspergillus spp., and can provide antifungal activity against some drug-resistant yeasts and moulds 77,78 . It even has potent antifungal activity in vitro against moulds that are difficult to treat, such as Fusarium spp.…”

Thematic Review Series: Glycosylphosphatidylinositol (GPI) Anchors: Biochemistry and Cell Biology Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling

“…Importantly, the compound seems to be fungal specifi c and does not inhibit mammalian GPI inositol acylase PIG-W activity ( 194 ). In vivo effi cacy of this agent has been demonstrated after oral administration in a murine model against candidiasis, aspergillosis, and fusariosis ( 189,195 ). Another group reported that a different compound, gepinacin, also inhibited Gwt1p activity ( 196 ).…”