靶向糖基化磷脂酰肌醇生物合成的抗真菌药物研究进展

抗真菌药物研究的两大策略,一是改造氮唑类或棘白菌素类抗真菌药物分子产生“Me Better”的新药分子,二是发现作用于新靶点的全新结构的“First in Class”的原创新药。后者已进入临床研究阶段的重要原创候选药物有靶向Sec14 的Turbinmicin、靶向糖基化磷脂酰肌醇（glycosylphosphatidylinositol,GPI）锚定蛋白合成转运的氨基吡啶类化合物,靶向二氢乳清酸脱氢酶（dihydroorotate dehydrogenase,DHODH）的F901318等。其中GPI锚定蛋白合成转运途径药物的发现已有10多年历史,研究比较充分,且具有广谱高效抗真菌和增强宿主抗真菌免疫反应的双重作用,本文主要综述靶向GPI生物合成的抗真菌药物的研究进展。

Research progress of antifungal drugs targeting glycosylphosphatidylinositol biosynthesis pathway

There are two strategies for antifungal drug research： to optimize azoles or echinocandins to produce new drug molecules of “Me Better” and to find new drugs of “First in Class” with new structures that act on new targets. The important original drug candidates that have entered the clinical trials include turbinmicin targeting Sec14, aminopyridines targeting glycosylphosphatidylinositol （GPI） anchor proteins synthesis and transport, and F901318 targeting dihydroorotate dehydrogenase （DHODH）. Among them, the discovery of drugs acting on GPI anchored the drugs synthesis and transport pathway has more than ten years of history. The research is relatively sufficient and has the dual effects of broad antifungal spectrum and enhancing host antifungal immune response. This paper mainly reviews the research progress of antifungal drugs targeting GPI biosynthesis pathway.