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PC1244 demonstrated potent antifungal activities against clinical\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            isolates (\n            <jats:italic>n<\/jats:italic>\n            = 96) with a MIC range of 0.016 to 0.25 \u03bcg\/ml, whereas the MIC range for voriconazole was 0.25 to 0.5 \u03bcg\/ml. PC1244 was a strong tight-binding inhibitor of recombinant\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            CYP51A and CYP51B (sterol 14\u03b1-demethylase) enzymes and strongly inhibited ergosterol synthesis in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            with a 50% inhibitory concentration of 8 nM. PC1244 was effective against a broad spectrum of pathogenic fungi (MIC range, &lt;0.0078 to 2 \u03bcg\/ml), especially\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            . PC1244 also proved to be quickly absorbed into both\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            hyphae and bronchial epithelial cells, producing persistent antifungal effects. In addition, PC1244 showed fungicidal activity (minimum fungicidal concentration, 2 \u03bcg\/ml) which indicated that it was 8-fold more potent than voriconazole.\n            <jats:italic>In vivo<\/jats:italic>\n            , once-daily intranasal administration of PC1244 (3.2 to 80 \u03bcg\/ml) to temporarily neutropenic, immunocompromised mice 24 h after inoculation with itraconazole-susceptible\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            substantially reduced the fungal load in the lung, the galactomannan concentration in serum, and circulating inflammatory cytokine levels. Furthermore, 7 days of extended prophylaxis with PC1244 showed\n            <jats:italic>in vivo<\/jats:italic>\n            effects superior to those of 1 day of prophylactic treatment, suggesting accumulation of the effects of PC1244. Thus, PC1244 has the potential to be a novel therapy for the treatment of\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            infection in the lungs of humans.\n          <\/jats:p>","DOI":"10.1128\/aac.01941-17","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T14:58:04Z","timestamp":1518188284000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection"],"prefix":"10.1128","volume":"62","author":[{"given":"Thomas","family":"Colley","sequence":"first","affiliation":[{"name":"Pulmocide Ltd., London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurpreet","family":"Sehra","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd., London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuradha","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-7186","authenticated-orcid":false,"given":"Yasuo","family":"Kizawa","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, Funabashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darius","family":"Armstrong-James","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Royal Brompton Hospital, London, United Kingdom"},{"name":"National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-6402","authenticated-orcid":false,"given":"Matthew C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Imperial College School of Public Health, St. Mary's Campus, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G. 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