{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:58:16Z","timestamp":1791921496846,"version":"4.3.4"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T00:00:00Z","timestamp":1477008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Fungal infections pose a significant public health burden with high morbidity and mortality. CD101 is a novel echinocandin under development for the treatment and prevention of systemic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>infections. Preclinical studies were conducted to evaluate the metabolic stability, plasma protein binding, pharmacokinetics, toxicity, and efficacy of CD101 at various dose levels. CD101 was stable to biotransformation in rat, monkey, and human liver microsomes and rat, monkey, dog, and human hepatocytes.<jats:italic>In vitro<\/jats:italic>studies suggest minimal interaction with recombinant cytochrome P450 enzymes (50% inhibitory concentrations [IC<jats:sub>50<\/jats:sub>s] of &gt;10 \u03bcM). Similar to anidulafungin, CD101 bound avidly (&gt;98%) to human, mouse, rat, and primate plasma proteins. In a 2-week repeat-dose comparison study, CD101 was well tolerated in rats (no effects on body weight, hematology, coagulation, or urinalysis). In contrast, administration of anidulafungin (at comparable exposure levels) resulted in reduced body weight, decreases in red blood cell, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, platelet, and reticulocyte counts, increases in neutrophil and eosinophil counts, polychromasia, and decreased activated partial thromboplastin time. Elevated plasma transaminases, total bilirubin, cholesterol, and globulin, dark and enlarged spleens, and single-cell hepatocyte necrosis were also observed for anidulafungin but not CD101. Hepatotoxicity may be due to the inherent chemical lability of anidulafungin generating potentially reactive intermediates. A glutathione trapping experiment confirmed the formation of a reactive species from anidulafungin, whereas CD101 did not exhibit instability or reactive intermediates. CD101 showed antifungal activity against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus<\/jats:named-content>infections in neutropenic mice. These preclinical studies demonstrated that CD101 is chemically and metabolically stable, well tolerated with no hepatotoxicity, and efficacious as an antifungal agent.<\/jats:p>","DOI":"10.1128\/aac.00701-16","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T01:59:02Z","timestamp":1473731942000},"page":"6872-6879","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":126,"title":["Preclinical Evaluation of the Stability, Safety, and Efficacy of CD101, a Novel Echinocandin"],"prefix":"10.1128","volume":"60","author":[{"given":"Voon","family":"Ong","sequence":"first","affiliation":[{"name":"Cidara Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grayson","family":"Hough","sequence":"additional","affiliation":[{"name":"Cidara Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schlosser","sequence":"additional","affiliation":[{"name":"Cidara Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Bartizal","sequence":"additional","affiliation":[{"name":"Cidara Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Balkovec","sequence":"additional","affiliation":[{"name":"Cidara Therapeutics, Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D.","family":"James","sequence":"additional","affiliation":[{"name":"Seachaid Pharmaceuticals, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Radha","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Seachaid Pharmaceuticals, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/599039"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1194"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/596757"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/11585270-000000000-00000"},{"key":"e_1_3_2_6_2","unstructured":"Merck & Co Inc. April 2016. Cancidas (caspofungin acetate) full prescribing information. http:\/\/www.merck.com\/product\/usa\/pi_circulars\/c\/cancidas\/cancidas_pi.pdf. Accessed 14 September 2016."},{"key":"e_1_3_2_7_2","unstructured":"Pfizer Inc. November 2013. Eraxis (anidulafungin) full prescribing information. http:\/\/labeling.pfizer.com\/showlabeling.aspx?id=566. 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Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"3"},{"key":"e_1_3_2_13_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement","author":"CLSI","year":"2012","unstructured":"CLSI. 2012. M27-S4. Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_14_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard","author":"CLSI","year":"2008","unstructured":"CLSI. 2008. M38-A2. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920007782798207"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20012"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S0026-895X(24)12040-8","article-title":"Measurement of fraction unbound paclitaxel in human plasma","volume":"28","author":"Brouwer E1","year":"2000","unstructured":"Brouwer E1, Verweij J, De Bruijn P, Loos WJ, Pillay M, Buijs D, Sparreboom A. 2000. Measurement of fraction unbound paclitaxel in human plasma. 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