Manjunatha, Ujjini H.; Vinayak, Sumiti; Zambriski, Jennifer A.; Chao, Alexander T.; Sy, Tracy; Noble, Christian G.; Bonamy, Ghislain M. C.; Kondreddi, Ravinder R.; Zou, Bin; Gedeck, Peter; Brooks, Carrie F.; Herbert, Gillian T.; Sateriale, Adam; Tandel, Jayesh; Noh, Susan; Lakshminarayana, Suresh B.; Lim, Siau H.; Goodman, Laura B.; Bodenreider, Christophe; Feng, Gu; Zhang, Lijun; Blasco, Francesca; Wagner, Juergen; Leong, F. Joel; Striepen, Boris; Diagana, Thierry T. published the artcile< A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis>, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is Cryptosporidium phosphatidylinositol kinase inhibitor preparation cryptosporidiosis diarrhea.
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiol. 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 clin. 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 preclin. evaluation as a drug candidate for the treatment of cryptosporidiosis.
Nature (London, United Kingdom) published new progress about Antidiarrheals. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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