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

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Abstract

The 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 echinocandin-resistant 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. Microorganisms must attach to host cell surfaces prior to col-onization, replication, and penetration through mucosal barriers. Glycosylphosphatidylinositol (GPI)-anchored proteins are known to serve as adhesins (1), and some fungal adhesins are derived from GPI-anchored proteins (2–5). E1210 is a broad-spectrum investigational antifungal agent that inhibits inositol acyltransferase, thereby preventing GPI-anchored protein matu-ration (6). This agent has potent in vitro activity against different pathogenic fungi, including Candida, Aspergillus, Fusarium, and Scedosporium species (6–10), and inhibition of inositol acyltrans-ferase by E1210 appears to be fungus specific (11). Animal model

Year: 2016
OAI identifier: oai:CiteSeerX.psu:10.1.1.958.389
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