基于新靶点的抗真菌药物研究进展

摘要

Invasive fungal infections are devastating with increasing morbidity and substantial mortality.Unfortunately,classic anti⁃fungal agents are limited by their antifungal spectrums,adverse effects,drug⁃drug interactions,variable pharmacokinetics,and limit types of formulation.Therefore,novel antifungal agents are urgently needed for the treatment of serious invasive fungal infections.It is possible that antifungal agents with novel targets will provide favorable options to treat fungal infections.It has made great development in antifungal agents research recent years,and the exciting advances are represented by four clusters of antifungal candidates.The first is the novel approach of candidates that destroy fungal cell walls,like E1210 and D11⁃2040.The second important finding is the can⁃didates that block protein kinases signaling pathways or protein phosphatase signaling pathways,such as KP⁃372⁃1,17⁃AAG,and My⁃cograb;The third area pertains to candidates that target fungal virulence factors,like C7,213Bi⁃18B7,188Re⁃18B7 and so on.The fourth is the candidates that activate the host immune system,including PEV7 andβ⁃(Man)3⁃Fba⁃TT.Over all,these four areas demonstrate the exciting research progress on new targets of antifungal agents.%侵袭性真菌感染的发病率正逐年上升。现有抗真菌药物由于抗菌谱有限、副作用大等原因，致使临床应用受限。因此，基于新靶点的抗真菌药物成为治疗真菌感染的迫切需要。近年来，抗真菌药物研究取得较大进展。其中，抑制真菌细胞壁合成的药物（如E1210和D11⁃2040）、抑制蛋白激酶或蛋白磷酸酶信号通路的药物（如KP⁃372⁃1、17⁃AAG、Mycograb）、靶向真菌毒力因子的单克隆抗体（如C7、213 Bi⁃18B7、188 Re⁃18B7）、激活宿主免疫系统的疫苗[如PEV7和β⁃（ Man）3⁃Fba⁃TT]等，正引起人们的关注。