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《Mycosystema》 2018-10
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The research progress of novel antifungal drug targets

ZHANG Jing-Xiang;YAN Lan;JIANG Yuan-Ying;Center of New Drug Research, School of Pharmacy, Second Military Medical University;  
In the past three decades, the incidence of invasive fungal infections has continued to rise, and the mortality rate remains high. The limited therapeutic drugs are one of the important factors that contribute to its high mortality rate. The discovery of new targets and new antifungal drugs has become an urgent need. The new antifungal targets under development can be summed up as following aspects:(1) Signal pathway-mediated antifungal targets, including calcineurin and its molecular chaperone Hsp90, 3-phosphoinositide-dependent protein kinase(PKH), and the enzymes that modify Ras protein, etc. Their antagonists include analogues of traditional immunosuppressants and antibodies to Hsp90, KP-372-1 and PS77, and leucomycin A etc;(2) The catalytic enzymes of GPI-anchored protein synthesis pathways. Their inhibitors include E1210 and M720;(3) Secreted aspartic proteases which can be inhibeted by special peptides, retrovirus inhibitors, and sulfone derivatives;(4) The two key enzymes, Tps1 and Tps2, of the trehalose synthesis. In consideration of invasive fungal infections seriously affect public health, and the development of new antifungal drugs relies on the exploration of new targets, therefore, this review aims at this core clinical problem and systematically introduces the current development of new antifungal drug targets, and provides the views on the feasibility of target selection and drug development strategies.
【Fund】: 上海市自然科学基金(17ZR1437700)~~
【CateGory Index】: R978.5
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