In vitro activity of APX2041, a new GWT1-inhibitor and in vivo efficacy of the prodrug APX2104 against Aspergillus fumigatus
Antimicrob Agents Chemother. 2021 Jul 26:AAC0068221. doi: 10.1128/AAC.00682-21. Online ahead of print.
Invasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as a potentially promising therapeutic against IA.