The antifungal pipeline: a reality check.

The antifungal pipeline: a reality check.
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DOI:
10.1038/nrd.2017.46
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发表时间:
2017-09
期刊:
Nature reviews. Drug discovery
影响因子:
--
通讯作者:
Perfect JR
Perfect JR
中科院分区:
其他
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--
作者:
Perfect JR

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随着世界免疫功能低下人口的增加,侵袭性真菌感染继续以创纪录的数量出现,部分原因是感染艾滋病毒的人数增加,部分原因是严重的潜在疾病得到了成功治疗。目前的抗真菌疗法-多烯类、氟胞嘧啶、唑类和棘白菌素类(作为单一疗法或预防性联合疗法,或作为经验性、先发制人或特异性疗法)-在这些感染的管理中的有效性已趋于稳定。虽然这些药物在临床上是有用的,但它们有几个局限性,如脱靶毒性,耐药真菌现在正在出现。因此,需要新的抗真菌药物。在这篇综述中,我讨论了强大的和动态的抗真菌管道,包括从临床前学术工作到制药工业产品的结果,并描述了目标,策略,化合物和潜在的结果。
Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies — polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) — in the management of these infections has plateaued. Although these drugs are clinically useful, they have several limitations, such as off-target toxicity, and drug-resistant fungi are now emerging. New antifungals are therefore needed. In this Review, I discuss the robust and dynamic antifungal pipeline, including results from preclinical academic efforts through to pharmaceutical industry products, and describe the targets, strategies, compounds and potential outcomes.
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