In Vitro Activity of APX2041, a New Gwt1 Inhibitor, and In Vivo Efficacy of the Prodrug APX2104 against Aspergillus fumigatus

Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0068221. doi: 10.1128/AAC.00682-21. Epub 2021 Jul 26.


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.

Keywords: APX001; APX001A; APX2041; APX2104; Aspergillus fumigatus; Gwt1; fosmanogepix; invasive aspergillosis; manogepix; murine model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Aspergillus fumigatus*
  • Drug Resistance, Fungal / genetics
  • Isoxazoles
  • Mice
  • Microbial Sensitivity Tests
  • Prodrugs* / pharmacology


  • Antifungal Agents
  • Isoxazoles
  • Prodrugs