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

ABSTRACT: 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.

SUBMITTER: Shaheen SK 

PROVIDER: S-EPMC8448089 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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<i>In Vitro</i> Activity of APX2041, a New Gwt1 Inhibitor, and <i>In Vivo</i> Efficacy of the Prodrug APX2104 against Aspergillus fumigatus.

Shaheen Shareef K SK   Juvvadi Praveen R PR   Allen John J   Shwab E Keats EK   Cole D Christopher DC   Asfaw Yohannes G YG   Kapoor Mili M   Shaw Karen Joy KJ   Steinbach William J WJ  

Antimicrobial agents and chemotherapy 20210726 10

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 <i>in vitro</i>. APX2104 treatment <i>in vivo</i> significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-res  ...[more]

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