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药物再利用和优化用于发现新型抗真菌药物。

Repurposing and optimization of drugs for discovery of novel antifungals.

机构信息

Edward. A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, MO, USA; Saint Louis University Institute for Drug and Biotherapeutic Innovation, USA.

Department of Chemistry, Saint Louis University, St Louis, MO, USA; Saint Louis University Institute for Drug and Biotherapeutic Innovation, USA.

出版信息

Drug Discov Today. 2022 Jul;27(7):2008-2014. doi: 10.1016/j.drudis.2022.04.021. Epub 2022 Apr 27.

Abstract

Although fungal diseases are a major and growing public health concern, there are only four major classes of drug to treat primary fungal pathogens. The pipeline of new antifungals in clinical development is relatively thin compared with other disease classes. One approach to rapidly identify and provide novel treatment options is to repurpose existing drugs as antifungals. However, such proposed drug-repurposing candidates often suffer suboptimal efficacy and pharmacokinetics (PK) for fungal diseases. Herein, we briefly review the current antifungal drug pipeline and recent approaches to optimize existing drugs into novel molecules with unique modes of action relative to existing antifungal drug classes.

摘要

虽然真菌病是一个主要且日益严重的公共卫生问题,但仅有四类主要药物可用于治疗主要真菌病原体。与其他疾病类别相比,临床开发中的新型抗真菌药物数量相对较少。一种快速识别和提供新型治疗方案的方法是将现有药物重新用于抗真菌药物。然而,此类被提议的药物再利用候选药物在治疗真菌病时往往疗效和药代动力学(PK)欠佳。在此,我们简要回顾了当前的抗真菌药物管线,以及最近优化现有药物成为具有独特作用模式的新型分子的方法,这些新型分子与现有的抗真菌药物类别相比具有独特的作用模式。

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