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PC945 was characterized as a potent, tightly binding inhibitor of\n                    <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n                    sterol 14\u03b1-demethylase (CYP51A and CYP51B) activity (50% inhibitory concentrations [IC\n                    <jats:sub>50<\/jats:sub>\n                    s], 0.23 \u03bcM and 0.22 \u03bcM, respectively) with characteristic type II azole binding spectra. Against 96 clinically isolated\n                    <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n                    strains, the MIC values of PC945 ranged from 0.032 to &gt;8 \u03bcg\/ml, while those of voriconazole ranged from 0.064 to 4 \u03bcg\/ml. Spectrophotometric analysis of the effects of PC945 against itraconazole-susceptible and -resistant\n                    <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n                    growth yielded IC\n                    <jats:sub>50<\/jats:sub>\n                    (determined based on optical density [OD]) values of 0.0012 to 0.034 \u03bcg\/ml, whereas voriconazole (0.019 to &gt;1 \u03bcg\/ml) was less effective than PC945. PC945 was effective against a broad spectrum of pathogenic fungi (with MICs ranging from 0.0078 to 2 \u03bcg\/ml), including\n                    <jats:named-content content-type=\"genus-species\">Aspergillus terreus<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Trichophyton rubrum<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Candida glabrata<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Candida krusei<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus gattii<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    , and\n                    <jats:named-content content-type=\"genus-species\">Rhizopus oryzae<\/jats:named-content>\n                    (1 or 2 isolates each). In addition, when\n                    <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n                    hyphae or human bronchial cells were treated with PC945 and then washed, PC945 was found to be absorbed quickly into both target and nontarget cells and to produce persistent antifungal effects. Among temporarily neutropenic immunocompromised mice infected with\n                    <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n                    intranasally, 50% of the animals survived until day 7 when treated intranasally with PC945 at 0.56 \u03bcg\/mouse, while posaconazole showed similar effects (44%) at 14 \u03bcg\/mouse. This profile affirms that topical treatment with PC945 should provide potent antifungal activity in the lung.\n                  <\/jats:p>","DOI":"10.1128\/aac.02280-16","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T20:30:22Z","timestamp":1487709022000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":86,"title":["<i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection"],"prefix":"10.1128","volume":"61","author":[{"given":"Thomas","family":"Colley","sequence":"first","affiliation":[{"name":"Pulmocide Ltd., London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Alanio","sequence":"additional","affiliation":[{"name":"Institut Pasteur, CNRS, Molecular Mycology Unit, French National Reference Center for Invasive Mycoses &amp; Antifungals, URA3012, Paris, France"},{"name":"Paris Diderot, Sorbonne Paris Cit\u00e9 University, Paris, France"},{"name":"Parasitology-Mycology Laboratory, Saint Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris (APHP), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet","family":"Sehra","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd., London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Kizawa","sequence":"additional","affiliation":[{"name":"Nihon University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G. 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