In Vitro Activity of APX2041, a New Gwt1 Inhibitor, and In Vivo Efficacy of the Prodrug APX2104 against Aspergillus fumigatus.
In Vitro Activity of APX2041, a New Gwt1 Inhibitor, and In Vivo Efficacy of the Prodrug APX2104 against Aspergillus fumigatus.
复制标题
新型 Gwt1 抑制剂 APX2041 的体外活性，以及前药 APX2104 对烟曲霉的体内功效。
DOI：
10.1128/aac.00682-21
复制
发表时间：
2021
影响因子：
4.9
通讯作者：
Steinbach,WilliamJ
中科院分区：
文献类型：
--
作者：
Shaheen,ShareefK;Juvvadi,PraveenR;Allen4th,John;Shwab,EKeats;Cole,DChristopher;Asfaw,YohannesG;Kapoor,Mili;Shaw,KarenJoy;Steinbach,WilliamJ
烟曲霉引起的侵袭性曲霉病（IA）是一种致命的感染，需要新的抗真菌治疗。在这里，我们证明了Gwt1抑制剂APX2041及其前药APX2104对烟曲霉的有效性。野生型、耐唑型和耐棘白菌素型烟曲霉对apx2041的体外敏感性相同。APX2104在体内显著延长了野生型和唑耐药菌株攻击的中性粒细胞减少小鼠的存活时间，表明APX2104是一种潜在的治疗IA的有前景的药物。
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 APX2041in vitro. APX2104 treatmentin vivosignificantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as a potentially promising therapeutic against IA.