Perfect John R
Duke University Medical Center, 200 Trent Drive, Durham, North Carolina 27710, USA.
Nat Rev Drug Discov. 2017 Sep;16(9):603-616. doi: 10.1038/nrd.2017.46. Epub 2017 May 12.
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.
随着全球免疫功能低下人群数量的增加，侵袭性真菌感染的病例数持续创下新高，部分原因是感染艾滋病毒的人数增多，部分原因是严重基础疾病的成功治疗。目前的抗真菌疗法——多烯类、氟胞嘧啶、唑类和棘白菌素类（作为单一疗法或联合用于预防，或作为经验性、先发制性或特异性疗法）——在治疗这些感染方面的效果已趋于平稳。尽管这些药物在临床上有用，但它们有几个局限性，如脱靶毒性，而且耐药真菌正在出现。因此需要新的抗真菌药物。在这篇综述中，我讨论了丰富且动态发展的抗真菌药物研发进程，包括从临床前学术研究成果到制药行业产品，并描述了靶点、策略、化合物和潜在结果。
