{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:15:21Z","timestamp":1787163321687,"version":"build-2736575974"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n                    , retained its\n                    <jats:italic>in vitro<\/jats:italic>\n                    potency (MIC\n                    <jats:sub>50<\/jats:sub>\n                    of \u22640.015 and MIC\n                    <jats:sub>90<\/jats:sub>\n                    of 0.12 \u03bcg\/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC\n                    <jats:sub>50<\/jats:sub>\n                    of 8 and MIC\n                    <jats:sub>90<\/jats:sub>\n                    of 64 \u03bcg\/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters\/kg), high oral absorption (73%), and a long half-life (&gt;48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg\/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 \u03bcg\/ml) but fully sensitive\n                    <jats:italic>in vitro<\/jats:italic>\n                    to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 \u03bcg\/ml) and moderately resistant to fluconazole (MIC of 8 \u03bcg\/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 \u03bcg\/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the\n                    <jats:italic>in vitro<\/jats:italic>\n                    MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC.\n                  <\/jats:p>","DOI":"10.1128\/aac.00185-15","type":"journal-article","created":{"date-parts":[[2015,6,29]],"date-time":"2015-06-29T22:44:58Z","timestamp":1435617898000},"page":"5567-5573","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis"],"prefix":"10.1128","volume":"59","author":[{"given":"E. P.","family":"Garvey","sequence":"first","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. J.","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. J.","family":"Schotzinger","sequence":"additional","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Sobel","sequence":"additional","affiliation":[{"name":"Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Lilly","sequence":"additional","affiliation":[{"name":"LSU Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"P. L.","family":"Fidel","sequence":"additional","affiliation":[{"name":"LSU Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60917-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2008.12.020"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/859071"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(12)90722-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-006-0023-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-11-169"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2007.tb01313.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.1.2.187"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2002.01142.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033114"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/sti.77.3.179"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31827307b2"},{"key":"e_1_3_2_14_2","first-page":"423","article-title":"Candida glabrata: an emergent opportunist in vulvovaginitis","volume":"77","author":"Buitr\u00f3n Garc\u00eda-Figueroa R","year":"2009","unstructured":"Buitr\u00f3n Garc\u00eda-Figueroa R, Araiza-Santibanez J, Basurto-Kuba E, Bonitaz-Trujillo A. 2009. Candida glabrata: an emergent opportunist in vulvovaginitis. Cir Cir 77:423\u2013427.","journal-title":"Cir Cir"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4103\/0377-4929.118703"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.5.2155-2162.2005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.05.068"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03707-14"},{"key":"e_1_3_2_19_2","volume-title":"CLSI document M27-A3","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, 3rd ed. CLSI document M27-A3. 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