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- W4377020647 abstract "<b>Abstract ID 24584</b> <b>Poster Board 515</b> Cryptosporidiosis is a neglected diarrheal disease that is caused by infection of the intestine by the parasite <i>Cryptosporidium</i>. This disease disproportionately afflicts young and malnourished children in low-middle income countries resulting 132,000 deaths annually, greatly exceeding that of all other recognized neglected tropical diseases. The only FDA-approved therapeutic, nitazoxanide, is only marginally effective in malnourished children (34% improvement versus placebo) and is ineffective in immunocompromised adults. To address this significant unmet medical need, we have conducted screening of known anti-<i>Plasmodium</i> compounds and other advanced clinical candidates for leads for the development of novel anti-<i>Cryptosporidium</i> therapeutics. Three series of compounds, each with a unique mode of action, have been advanced to medicinal chemistry optimization. The most potent compounds identified to date have EC<sub>50</sub>values ranging from 70-200 nM in HCT-8 cells infected with <i>C. parvum</i>. Compounds from each class have oral <i>in vivo</i> efficacy in an immunocompromised mouse model of <i>Cryptosporidium</i> infection, some at doses as low as 5 mg/kg BID. Ongoing efforts to identify a safe and potent therapeutic will be discussed. Research reported in this publication was supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers R01 AI143951, R33 AI141184, and R21 AI141184." @default.
- W4377020647 created "2023-05-19" @default.
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- W4377020647 date "2023-05-18" @default.
- W4377020647 modified "2023-09-28" @default.
- W4377020647 title "Discovery of Potent Therapeutics for Treatment of Cryptosporidiosis" @default.
- W4377020647 doi "https://doi.org/10.1124/jpet.122.245840" @default.
- W4377020647 hasPublicationYear "2023" @default.
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