ArticleNature2017
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
104 citing papers in PubMed, 195 citations in OpenAlex.
- A rapid sporozoite viability assay identifies leads and targetable enzymatic activities against the zoonotic Cryptosporidium parvum.International journal for parasitology. Drugs and drug resistance · 2026Article
- Phosphatidylinositol 4-kinase as a target of pathogens-friend or foe?FEBS letters · 2026Review
- Structure-Activity Relationship Study of Anti-Cryptosporidium Benzoxaboroles Yields Enhanced Potency and Curative Efficacy.Journal of medicinal chemistry · 2026Article
- Functional Characterization and Inhibition Analysis of a Glutathione Transferase fromPharmaceuticals (Basel, Switzerland) · 2026Article
- Genomic heterogeneity of NAD(P)H dehydrogenase predisposes Cryptosporidium to clofazimine resistance.Nature microbiology · 2026Article
- Insights into the lifecycle of Cryptosporidium and compounds targeting developmental stages.Current opinion in microbiology · 2026Review
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- High-Content Screening for Cryptosporidium Drug Discovery.Methods in molecular biology (Clifton, N.J.) · 2026Article
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- Pathogenicity and virulence ofVirulence · 2025Review
- Norditerpene Natural Products from Subterranean Fungi with Anti-Parasitic Activity.Microorganisms · 2025Article
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- Widespread genomic heterogeneity at the type II NAD(P)H dehydrogenase locus predisposesbioRxiv : the preprint server for biology · 2025Article
- Targeting translation initiation yields fast-killing therapeutics against the zoonotic parasite Cryptosporidium parvum.PLoS pathogens · 2025Article
- De-coupling immune parameters and toxicity associated with IL-12 agonism.Cell reports · 2025Article
- Medicinal Chemistry Progression of Sapanisertib, the Anticancer and DualJournal of medicinal chemistry · 2025Article
- Vesicular mechanisms of drug resistance in apicomplexan parasites.Microbiology and molecular biology reviews : MMBR · 2025Review
- In vitro molecular assessment ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Article
- Discovery of an Orally Efficacious Pyrazolo[3,4-Journal of medicinal chemistry · 2025Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.