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Nat Microbiol2024;9(11):2817-2835.November 1, 2024Journal Article

Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.

Ujjini H Manjunatha1, Suresh B Lakshminarayana2, Rajiv S Jumani2, Alexander T Chao2, Joseph M Young3, Jonathan E Gable2, Mark Knapp3, Imad Hanna4, Jean-Rene Galarneau5, John Cantwell3, Upendra Kulkarni6, Michael Turner3, Peichao Lu3, Kristen H Darrell2,7, Lucy C Watson2, Katherine Chan2, Debjani Patra2, Mulugeta Mamo3, Catherine Luu3, Carlos Cuellar3, Jacob Shaul3,8, Linda Xiao2, Ying-Bo Chen2, Shannon K Carney9,10, Jay Lakshman11, Colin S Osborne2, Jennifer A Zambriski9,12, Natasha Aziz2,13, Christopher Sarko3, Thierry T Diagana14
1Global Health, Biomedical Research, Novartis, Emeryville, CA, USA. manjunatha.ujjini@novartis.com.
2Global Health, Biomedical Research, Novartis, Emeryville, CA, USA.
3Biomedical Research, Novartis, Emeryville, CA, USA.
4Biomedical Research, Novartis, East Hanover, NJ, USA.
5Biomedical Research, Novartis, Cambridge, MA, USA.
6Novartis Pharmaceutical Corporation, Cambridge, MA, USA.
7Metagenomi, Inc., Emeryville, CA, USA.
8Absci Corporation, Vancouver, WA, USA.
9Department of Population Health Sciences, College of Veterinary Medicine, Center for One Health Research, Blacksburg, VA, USA.
10Cornell University, College of Veterinary Medicine, Department of Population Medicine and Diagnostic Sciences, Ithaca, NY, USA.
11Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
12Veterinarians for Global Solutions, Washington, DC, USA.
13Genentech Research and Early Development, South San Francisco, CA, USA.
14Global Health, Biomedical Research, Novartis, Emeryville, CA, USA. thierry.diagana@novartis.com.
PubMed PMC DOI PDF

Abstract

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By…

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