Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans

C-22 修饰的 FK520 类似物对新型隐球菌具有增强的真菌特异性和体内治疗效果

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作者:Angela Rivera, Won Young Lim #, Eunchong Park #, Patrick A Dome #, Michael J Hoy, Ivan Spasojevic, Sheng Sun, Anna Floyd Averette, Sergio Pina-Oviedo, Praveen R Juvvadi, William J Steinbach, Maria Ciofani, Jiyong Hong, Joseph Heitman

Abstract

Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human host. With rising resistance to the current antifungal arsenal and an increasing at-risk population, there is an urgent need for the development of new antifungal compounds. The FK520 analogs described in this study display potent antifungal activity as a novel class of antifungals centered on modifying an existing orally active FDA-approved therapy. This research advances the development of much-needed newer antifungal treatment options with novel mechanisms of action.

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