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发现了一系列具有单次疗效的新型化合物,可有效对抗幼年和成年血吸虫物种。

The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species.

机构信息

Salvensis, Sandwich, Kent, United Kingdom.

Department for Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

PLoS Negl Trop Dis. 2021 Jul 19;15(7):e0009490. doi: 10.1371/journal.pntd.0009490. eCollection 2021 Jul.

Abstract

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.

摘要

血吸虫病的治疗和控制依赖于一种名为吡喹酮的药物,但这种药物并不理想,原因有几个,包括对寄生虫幼体阶段的效力不足、剂量大小和耐药风险。我们通过高通量筛选优化了一系列化合物的性质,并设计了候选药物进行临床开发。最佳化合物在感染的小鼠模型中,单次口服剂量小于 10mg/kg 时,可清除幼年和成年曼氏血吸虫虫。该系列中的几种化合物有望在人类中通过单次口服剂量小于 5mg/kg 的剂量治疗多种物种的血吸虫病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32a9/8321398/e2be0df1d719/pntd.0009490.g001.jpg

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