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T-2307的综述,一种导致真菌线粒体膜电位崩溃的研究性药物。

Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential.

作者信息

Wiederhold Nathan P

机构信息

Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.

出版信息

J Fungi (Basel). 2021 Feb 11;7(2):130. doi: 10.3390/jof7020130.

Abstract

Invasive infections caused by that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non- species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by , as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against species, including , , and strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

摘要

对临床可用抗真菌药耐药的[具体病原体]引起的侵袭性感染日益受到关注。在多个大洲的多个国家,非[具体菌种]中氟康唑耐药率不断上升已有文献记载。在过去几年中,这种情况因[具体原因]而进一步恶化,因为这种新兴病原体的分离株往往对多种抗真菌药耐药。T-2307是一种目前正在开发用于治疗侵袭性真菌感染的芳香二脒。与哺乳动物细胞相比,该药物已显示出能选择性地导致酵母线粒体膜电位崩溃。已证明其对包括[具体菌种]、[具体菌种]和[具体菌种]菌株在内的[具体菌种]具有体外活性,这些菌株对唑类和棘白菌素类抗真菌药耐药。也有报道称其对[具体菌种]有活性,并且在侵袭性念珠菌病和隐球菌病的实验模型中已转化为体内疗效。然而,由于目前尚无涉及人类研究的已发表数据,关于该药物的临床疗效和安全性知之甚少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/7916847/20791c5f34c6/jof-07-00130-g001.jpg

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