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We have previously observed that 2\u2010deoxy\u2010<jats:sc>d<\/jats:sc>\u2010glucose (2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>) could inhibit both the enzyme activity of <jats:italic>C.\u00a0parvum<\/jats:italic> hexokinase (Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>) and the parasite growth in\u00a0vitro. However, the action and fate of 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content> in <jats:italic>C.\u00a0parvum<\/jats:italic> was not fully investigated. In the present study, we showed that, although 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content> could be phosphorylated by Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content> to form 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>\u20106\u2010phosphate (2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>6P), the anti\u2010cryptosporidial activity of 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content> was mainly attributed to the action of 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content> on Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>, rather than the action of 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content> or 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>6P on the downstream enzyme glucose\u20106\u2010phosphate isomerase (Cp<jats:styled-content style=\"fixed-case\">GPI<\/jats:styled-content>) nor 2<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>6P on Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>. These observations further supported the hypothesis that Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content> could serve as a drug target in the parasite. We also screened 1,200 small molecules consisting of marketed drugs against Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>, from which four drugs were identified as Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content> inhibitors with micromolar level of anti\u2010cryptospordial activities at concentrations nontoxic to the host cells (i.e. hexachlorphene, thimerosal, alexidine dihydrochloride, and ebselen with <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>\u00a0=\u00a00.53, 1.77, 8.1 and 165\u00a0\u03bcM, respectively). The anti\u2010Cp<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content> activity of the four existing drugs provided us new reagents for studying the enzyme properties of the parasite hexokinase.<\/jats:p>","DOI":"10.1111\/jeu.12690","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T13:37:02Z","timestamp":1537191422000},"page":"460-468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Action of the Hexokinase Inhibitor 2\u2010deoxy\u2010<scp>d<\/scp>\u2010glucose on <i>Cryptosporidium parvum<\/i> and the Discovery of Activities against the Parasite Hexokinase from Marketed Drugs"],"prefix":"10.1111","volume":"66","author":[{"given":"Rana","family":"Eltahan","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology College of Veterinary Medicine &amp; Biomedical Sciences Texas A&amp;M University College Station Texas 77843\u20104467"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengguang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology College of Veterinary Medicine &amp; Biomedical Sciences Texas A&amp;M University College Station Texas 77843\u20104467"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology College of Veterinary Medicine &amp; Biomedical Sciences Texas A&amp;M University College Station Texas 77843\u20104467"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0659","authenticated-orcid":false,"given":"Guan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology College of Veterinary Medicine &amp; Biomedical Sciences Texas A&amp;M University College Station Texas 77843\u20104467"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094786"},{"key":"e_1_2_6_3_1","first-page":"195","article-title":"Trials with Yomesan and other selected chemicals against Thysanosoma actinioides, the fringed tapeworm of sheep","volume":"34","author":"Allen R. 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