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In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection

Thomas Colley, Alexandre Alanio, Steven L. Kelly, Gurpreet Sehra, Yasuo Kizawa, Andrew G. S. Warrilow, Josie E. Parker, Diane E. Kelly, Genki Kimura, Lauren Anderson-Dring, Takahiro Nakaoki, Mihiro Sunose, Stuart Onions, Damien Crepin, Franz Lagasse, Matthew Crittall, Jonathan Shannon, Michael Cooke, Stéphane Bretagne, John King-Underwood, John Murray, Kazuhiro Ito, Pete Strong, Garth Rapeport

Antimicrobial Agents and Chemotherapy, Volume: 61, Issue: 5, Start page: e02280-16

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DOI (Published version): 10.1128/AAC.02280-16

Abstract

The profile of PC945, a novel triazole antifungal, designed for administration via inhalation, hasbeen assessed in a range of in vitro and in vivo studies. PC945 was characterized as a potent, tight-binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A and CYP51B)activity.In addi...

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Published in: Antimicrobial Agents and Chemotherapy
ISSN: 0066-4804 1098-6596
Published: 2017
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URI: https://cronfa.swan.ac.uk/Record/cronfa34336
Abstract: The profile of PC945, a novel triazole antifungal, designed for administration via inhalation, hasbeen assessed in a range of in vitro and in vivo studies. PC945 was characterized as a potent, tight-binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A and CYP51B)activity.In addition, when A. fumigatus hyphae or human bronchial cells were treated with PC945, and thenwashed, PC945 was found to be quickly absorbed into both target and non-target cells and toproduce persistent antifungal effects. In temporarily neutropenic immunocompromised miceinfected with A. fumigatus intranasally, 50% of the animals survived until day 7 when treatedintranasally with PC945 at 0.56 μg/mouse, while posaconazole showed similar effects (44%) at14 μg/mouse. This profile affirms that topical treatment with PC945 should provide potentantifungal activity in the lung.
College: Swansea University Medical School
Issue: 5
Start Page: e02280-16

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