Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in Candida Species
Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in Candida Species
复制标题
DOI：
10.1128/aac.01387-19
复制
发表时间：
2020-01-01
影响因子：
4.9
通讯作者：
Shaw, Karen Joy
中科院分区：
文献类型：
--
作者：
Kapoor, Mili;Moloney, Molly;Shaw, Karen Joy
Manogepix （MGX）靶向糖基磷脂酰肌醇生物合成途径早期肌醇酰化所需的保守真菌Gwt1酶。前药fosmanogepix目前正处于临床开发阶段，用于治疗侵袭性真菌感染。我们确定，在白色念珠菌、光秃念珠菌和旁裂念珠菌中，自发性突变导致MGX易感性降低的中位数频率范围为3 × 10（-8）至
Manogepix (MGX) targets the conserved fungal Gwt1 enzyme required for acylation of inositol early in the glycosylphosphatidylinositol biosynthesis pathway. The prodrug fosmanogepix is currently in clinical development for the treatment of invasive fungal infections. We determined that the median frequencies of spontaneous mutations conferring reduced susceptibility to MGX in Candida albicans, C. glabrata, and C. parapsilosis ranged from 3 x 10(-8) to