Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1016/j.enpol.2016.11.009 |
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis | |
Manjunatha, Ujjini H.1; Vinayak, Sumiti2; Zambriski, Jennifer A.3; Chao, Alexander T.1; Sy, Tracy3; Noble, Christian G.1; Bonamy, Ghislain M. C.1; Kondreddi, Ravinder R.1; Zou, Bin1; Gedeck, Peter1; Brooks, Carrie F.2; Herbert, Gillian T.2; Sateriale, Adam2; Tandel, Jayesh4; Noh, Susan3,5,6; Lakshminarayana, Suresh B.1; Lim, Siau H.1; Goodman, Laura B.7; Bodenreider, Christophe1; Feng, Gu; Zhang, Lijun8; Blasco, Francesca1; Wagner, Juergen; Leong, F. Joel1; Striepen, Boris2,4; Diagana, Thierry T.1 | |
2017-06-15 | |
发表期刊 | NATURE
![]() |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 546期号:7658页码:376-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Singapore; USA; Peoples R China |
英文摘要 | 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 effective treatment. 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000403250900029 |
WOS关键词 | RANDOMIZED CONTROLLED-TRIAL ; CHALLENGED DAIRY CALVES ; PLASMODIUM LIVER STAGES ; DEVELOPING-COUNTRIES ; MALARIA PARASITES ; ZAMBIAN CHILDREN ; PARVUM OOCYSTS ; ASSAYS ; NITAZOXANIDE ; ANTIMALARIAL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/16556 |
专题 | 气候变化 |
作者单位 | 1.Novartis Inst Trop Dis, 10 Biopolis Rd,05-01 Chromos, Singapore 138670, Singapore; 2.Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA; 3.Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA; 4.Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA; 5.Washington State Univ, USDA ARS, Anim Dis Res Unit, Pullman, WA 99164 USA; 6.Washington State Univ, Dept Vet Microbiol & Pathol, Washington Anim Dis Diagnost Lab, Pullman, WA 99164 USA; 7.Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA; 8.China Novartis Inst Biomed Res, Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Manjunatha, Ujjini H.,Vinayak, Sumiti,Zambriski, Jennifer A.,et al. A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis[J]. NATURE,2017,546(7658):376-+. |
APA | Manjunatha, Ujjini H..,Vinayak, Sumiti.,Zambriski, Jennifer A..,Chao, Alexander T..,Sy, Tracy.,...&Diagana, Thierry T..(2017).A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis.NATURE,546(7658),376-+. |
MLA | Manjunatha, Ujjini H.,et al."A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis".NATURE 546.7658(2017):376-+. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论