Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawbacks due to e.g. toxicity of the respective compounds or resistance to approved antitrypanosomal drugs. In this review, the different strategies of drug development against HAT are considered, namely the target-based approach, the phenotypic high throughput screening and the drug repurposing strategy. The most promising compounds emerging from these approaches entering an in vivo evaluation are mentioned herein. Of note, it may turn out to be difficult to confirm in vitro activity in an animal model of infection; however, possible reasons for the missing efficacy in unsuccessful in vivo studies are discussed.

中文翻译：

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在针对非洲昏睡病的临床前开发中的新型先导化合物

人类非洲锥虫病（HAT），也称为非洲昏睡病，是由锥虫属的寄生原生动物引起的。随着疾病的进展，如果不及时治疗，这些寄生虫会越过血脑屏障，对患者致命。由于例如各自化合物的毒性或对批准的抗胰体药物的抗性，当前的疗法具有若干缺点。在这篇综述中，考虑了针对HAT的药物开发的不同策略，即基于靶标的方法，表型高通量筛选和药物重用策略。这些方法产生的最有希望的化合物进入体内评价在本文中提及。值得注意的是，在感染的动物模型中可能难以确定其体外活性。然而，讨论了在不成功的体内研究中缺乏疗效的可能原因。