Antifungal Drugs: The Current Armamentarium and Development of New Agents
Antifungal Drugs: The Current Armamentarium and Development of New Agents
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DOI：
10.1128/microbiolspec.funk-0002-2016
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发表时间：
2016-10-01
影响因子：
3.7
通讯作者：
Cowen, Leah E.
中科院分区：
文献类型：
--
作者：
Robbins, Nicole;Wright, Gerard D.;Cowen, Leah E.
侵袭性真菌感染正在成为人类死亡和发病的一个日益重要的原因，特别是对于免疫功能低下的人群。真菌病原体白色念珠菌、新型隐球菌和烟曲霉每年共同导致超过100万人死亡。因此，安全有效的抗真菌治疗对现代医学实践的重要性从未如此之大。鉴于真菌是真核生物，就像它们的人类宿主一样，可用于药物开发的独特分子靶标的数量仍然有限。目前只有三类分子被批准用于治疗侵袭性真菌病。这些药剂的功效受到宿主毒性、真菌抑制活性或病原体群体中出现耐药性的影响。在这里，我们描述了我们目前的抗真菌药物库，并强调了目前正在采用的策略，以提高这些药物的治疗安全性和有效性。我们讨论了发现具有抗真菌活性的新型化学物质的最新方法，并强调了一些最有前途的抗真菌药物开发新靶点。我们将联合治疗的益处作为一种策略，以扩大我们目前的抗真菌药物库，并讨论已显示出最大的临床开发潜力的抗真菌药物组合。尽管近年来上市的新型抗真菌药物很少，但很明显，通过利用创新的药物发现方法和培养学术界和工业界之间的合作，有很大的潜力来支持抗真菌药物。
Invasive fungal infections are becoming an increasingly important cause of human mortality and morbidity, particularly for immunocompromised populations. The fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus collectively contribute to over 1 million human deaths annually. Hence, the importance of safe and effective antifungal therapeutics for the practice of modern medicine has never been greater. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for drug development remains limited. Only three classes of molecules are currently approved for the treatment of invasive mycoses. The efficacy of these agents is compromised by host toxicity, fungistatic activity, or the emergence of drug resistance in pathogen populations. Here we describe our current arsenal of antifungals and highlight current strategies that are being employed to improve the therapeutic safety and efficacy of these drugs. We discuss state-of-the-art approaches to discover novel chemical matter with antifungal activity and highlight some of the most promising new targets for antifungal drug development. We feature the benefits of combination therapy as a strategy to expand our current repertoire of antifungals and discuss the antifungal combinations that have shown the greatest potential for clinical development. Despite the paucity of new classes of antifungals that have come to market in recent years, it is clear that by leveraging innovative approaches to drug discovery and cultivating collaborations between academia and industry, there is great potential to bolster the antifungal armamentarium.