信息来源：
http://www.natureasia.com/zh-cn/nature/highlights/86624
https://www.nature.com/nature/journal/v546/n7658/full/nature22337.html

顶复门寄生虫隐孢子虫（Cryptosporidium）是小儿腹泻的主要病因，在婴儿和免疫力较弱的患者中死亡率较高。作者报告了一种隐孢子虫病药物筛选的工作流程，并发现吡唑并吡啶能作为隐孢子虫脂激酶PI(4)K 的选择性ATP竞争性抑制剂。主要候选药物KDU731能在体外抑制小隐孢子虫（C. parvum）和人隐孢子虫（C. hominis）的生长，且在免疫削弱小鼠和新生牛犊（一种人类疾病的临床模型）中表现出了体内疗效。KDU731还能满足一系列安全和药理标准，有望成为人们急需的隐孢子虫病治疗药物。

A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

Ujjini H. Manjunatha, Sumiti Vinayak, Jennifer A. Zambriski, Alexander T. Chao, Tracy Sy, Christian G. Noble, Ghislain M. C. Bonamy, Ravinder R. Kondreddi, Bin Zou, Peter Gedeck, Carrie F. Brooks, Gillian T. Herbert, Adam Sateriale, Jayesh Tandel, Susan Noh, Suresh B. Lakshminarayana, Siau H. Lim, Laura B. Goodman, Christophe Bodenreider, Gu Feng, Lijun Zhang, Francesca Blasco, Juergen Wagner, F. Joel Leong, Boris Striepen et al.

Nature 546, 376–380 (15 June 2017) doi:10.1038/nature22337

Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effectivetreatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.