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

頂復(fù)門寄生蟲隱孢子蟲（Cryptosporidium）是小兒腹瀉的主要病因，在嬰兒和免疫力較弱的患者中死亡率較高。作者報告了一種隱孢子蟲病藥物篩選的工作流程，并發(fā)現(xiàn)吡唑并吡啶能作為隱孢子蟲脂激酶PI(4)K 的選擇性ATP競爭性抑制劑。主要候選藥物KDU731能在體外抑制小隱孢子蟲（C. parvum）和人隱孢子蟲（C. hominis）的生長，且在免疫削弱小鼠和新生牛犢（一種人類疾病的臨床模型）中表現(xiàn)出了體內(nèi)療效。KDU731還能滿足一系列安全和藥理標準，有望成為人們急需的隱孢子蟲病治療藥物。

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.