{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:29:22Z","timestamp":1791980962140,"version":"4.4.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T00:00:00Z","timestamp":1490313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"SCYNEXIS, Inc."},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    SCY-078 (MK-3118) is a novel, semisynthetic derivative of enfumafungin and represents the first compound of the triterpene class of antifungals. SCY-078 exhibits potent inhibition of \u03b2-(1,3)-\n                    <jats:sc>d<\/jats:sc>\n                    -glucan synthesis, an essential cell wall component of many pathogenic fungi, including\n                    <jats:named-content content-type=\"genus-species\">Candida<\/jats:named-content>\n                    spp. and\n                    <jats:named-content content-type=\"genus-species\">Aspergillus<\/jats:named-content>\n                    spp. SCY-078 is currently in phase 2 clinical development for the treatment of invasive fungal diseases.\n                    <jats:italic>In vitro<\/jats:italic>\n                    disposition studies to assess solubility, intestinal permeability, and metabolic stability were predictive of good oral bioavailability. Preclinical pharmacokinetic studies were consistent with once-daily administration to humans. After intravenous delivery, plasma clearance in rodents and dogs was low, representing &lt;15% and &lt;25% of hepatic blood flow, respectively. The terminal elimination-phase half-life was 5.5 to 8.7 h in rodents, and it was \u223c9.3 h in dogs. The volume of distribution at steady-state was high (4.7 to 5.3 liters\/kg), a finding suggestive of extensive tissue distribution. Exposure of SCY-078 in kidney tissue, a target organ for invasive fungal disease such as candidiasis, exceeded plasma by 20- to 25-fold for the area under the concentration-time curve from 0 h to infinity (AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    . SCY-078 achieved efficacy endpoints following oral delivery across multiple murine models of disseminated candidiasis. The pharmacokinetic\/pharmacodynamic indices\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    \/MIC and AUC\/MIC correlated with outcome. Target therapeutic exposure, expressed as the plasma AUC\n                    <jats:sub>0\u201324<\/jats:sub>\n                    , was comparable across models, with an upper value of 11.2 \u03bcg\u00b7h\/ml (15.4 \u03bcM\u00b7h); the corresponding mean value for free drug AUC\/MIC was \u223c0.75. Overall, these results demonstrate that SCY-078 has the oral and intravenous (i.v.) pharmacokinetic properties and potency in murine infection models of disseminated candidiasis to support further investigation as a novel i.v. and oral treatment for invasive fungal diseases.\n                  <\/jats:p>","DOI":"10.1128\/aac.02068-16","type":"journal-article","created":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T21:50:39Z","timestamp":1485813039000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis"],"prefix":"10.1128","volume":"61","author":[{"given":"Stephen A.","family":"Wring","sequence":"first","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Randolph","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SeongHee","family":"Park","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Abruzzo","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Flattery","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graig","family":"Garrett","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Peel","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Outcalt","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall","family":"Powell","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Trucksis","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Angulo","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katyna","family":"Borroto-Esoda","sequence":"additional","affiliation":[{"name":"SCYNEXIS, Inc., Jersey City, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1194"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks466"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01588-12"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02145-13"},{"key":"e_1_3_2_6_2","article-title":"A phase I multiple-rising dose study evaluating safety, tolerability, and pharmacokinetics of MK-3118, oral glucan synthase inhibitor in healthy volunteers, abstr F1-1390","author":"Trucksis M","year":"2011","unstructured":"Trucksis M GarrettGBautmansAHeirmanILaethemMComisarWAMagantiLBiSIwamotoMO'MaraEWagnerJADepreMde HoonJ. 2011. 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