Departamento de Ciencias Biomédicas, Universidad de León, Campus de Vegazana, E-24071 León, Spain.
Departamento de Ciencias Biomédicas, Universidad de León, Campus de Vegazana, E-24071 León, Spain.
Drug Discov Today. 2019 May;24(5):1209-1216. doi: 10.1016/j.drudis.2019.03.007. Epub 2019 Mar 12.
The current commitment of the pharma industry, nongovernmental organizations and academia to find better treatments against neglected tropical diseases should end decades of challenge caused by these global scourges. The initial result of these efforts has been the introduction of enhanced combinations of drugs, currently in clinical use, or formulations thereof. Phenotypic screening based on intracellular parasite infections has been revealed as the first key tool of antileishmanial drug discovery, because most first-in-class drugs entering Phase I trials were discovered this way. The professional commitment among stakeholders has enabled the availability of a plethora of new chemical entities that fit the target product profile for these diseases. However, the rate of hit discovery in leishmaniasis is far behind that for other neglected diseases. This review defends the need to develop new screening methods that consider the part played not only by intracellular parasites but also by the host's immune system to generate disease-relevant assays and improve clinical outcomes.
制药行业、非政府组织和学术界目前致力于寻找更好的治疗方法来对抗被忽视的热带病，这应该结束这些全球祸害给人类带来的数十年的挑战。这些努力的初步成果是引入了目前正在临床使用的改良药物组合或其制剂。基于细胞内寄生虫感染的表型筛选已被证明是抗利什曼病药物发现的第一个关键工具，因为进入 I 期临床试验的大多数首创药物都是通过这种方式发现的。利益相关者的专业承诺使大量符合这些疾病目标产品特性的新化学实体得以问世。然而，利什曼病的命中发现率远远落后于其他被忽视的疾病。这篇综述认为有必要开发新的筛选方法，这些方法不仅要考虑细胞内寄生虫的作用，还要考虑宿主免疫系统的作用，以生成与疾病相关的检测方法并改善临床结果。
