{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:49:59Z","timestamp":1789627799204,"version":"build-2803163510"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI094098"],"award-info":[{"award-number":["AI094098"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptosporidium parvum<\/jats:named-content>\n            might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            CDPK1 and block\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            growth in tissue culture\n            <jats:italic>in vitro<\/jats:italic>\n            . Although these compounds potently inhibited kinase activity\n            <jats:italic>in vitro<\/jats:italic>\n            , most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma gondii<\/jats:named-content>\n            , where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            that are worthy of further exploration.\n          <\/jats:p>","DOI":"10.1128\/aac.01915-15","type":"journal-article","created":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T04:09:28Z","timestamp":1447128568000},"page":"570-579","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1)\n            <i>In Vitro<\/i>\n            by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture"],"prefix":"10.1128","volume":"60","author":[{"given":"Theresa B.","family":"Kuhlenschmidt","sequence":"first","affiliation":[{"name":"Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentine U.","family":"Rutaganira","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojun","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keliang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevan M.","family":"Shokat","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Kuhlenschmidt","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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