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The drug of choice in treating PAM is the antifungal antibiotic amphotericin B, but its use is associated with severe adverse effects. Moreover, few patients treated with amphotericin B have survived PAM. Therefore, fast-acting and efficient drugs are urgently needed for the treatment of PAM. To facilitate drug screening for this pathogen, an automated, high-throughput screening methodology was developed and validated for the closely related species\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Naegleria gruberi<\/jats:named-content>\n                    . Five kinase inhibitors and an NF-kappaB inhibitor were hits identified in primary screens of three compound libraries. Most importantly for a preclinical drug discovery pipeline, we identified corifungin, a water-soluble polyene macrolide with a higher activity against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Naegleria<\/jats:named-content>\n                    than that of amphotericin B. Transmission electron microscopy of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. fowleri<\/jats:named-content>\n                    trophozoites incubated with different concentrations of corifungin showed disruption of cytoplasmic and plasma membranes and alterations in mitochondria, followed by complete lysis of amebae.\n                    <jats:italic>In vivo<\/jats:italic>\n                    efficacy of corifungin in a mouse model of PAM was confirmed by an absence of detectable amebae in the brain and 100% survival of mice for 17 days postinfection for a single daily intraperitoneal dose of 9 mg\/kg of body weight given for 10 days. The same dose of amphotericin B did not reduce ameba growth, and mouse survival was compromised. Based on these results, the U.S. FDA has approved orphan drug status for corifungin for the treatment of PAM.\n                  <\/jats:p>","DOI":"10.1128\/aac.00643-12","type":"journal-article","created":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T22:49:14Z","timestamp":1344293354000},"page":"5450-5457","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["Corifungin, a New Drug Lead against Naegleria, Identified from a High-Throughput Screen"],"prefix":"10.1128","volume":"56","author":[{"given":"Anjan","family":"Debnath","sequence":"first","affiliation":[{"name":"Sandler Center for Drug Discovery, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefino B.","family":"Tunac","sequence":"additional","affiliation":[{"name":"Acea Biotech, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Galindo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Silva-Olivares","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineko","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Sandler Center for Drug Discovery, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/S0140-6736(72)90772-6","article-title":"Primary amoebic meningoencephalitis","author":"Anderson K","year":"1972","unstructured":"AndersonK JamiesonA. 1972. 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