{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:08:38Z","timestamp":1790712518885,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"NSF","award":["NSF-MCB-09020212"],"award-info":[{"award-number":["NSF-MCB-09020212"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cryptococcosis is a life-threatening disease often associated with HIV infection. Three\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus<\/jats:named-content>\n                    species CYP51 enzymes were purified and catalyzed the 14\u03b1-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [\n                    <jats:italic>\n                      K\n                      <jats:sub>d<\/jats:sub>\n                    <\/jats:italic>\n                    ] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (\n                    <jats:italic>\n                      K\n                      <jats:sub>d<\/jats:sub>\n                    <\/jats:italic>\n                    range, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (\n                    <jats:italic>\n                      K\n                      <jats:sub>d<\/jats:sub>\n                    <\/jats:italic>\n                    , 4.53 \u03bcM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC\n                    <jats:sub>50<\/jats:sub>\n                    ] range, 0.14 to 0.20 \u03bcM), while it only weakly inhibited human CYP51 activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    , \u223c600 \u03bcM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol\/obtusifoliol in the cell membranes.\n                  <\/jats:p>","DOI":"10.1128\/aac.00349-16","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T23:05:16Z","timestamp":1462835116000},"page":"4530-4538","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme"],"prefix":"10.1128","volume":"60","author":[{"given":"Andrew G. 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