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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
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spelling 2017-07-26T11:19:56Z v2 34336 2017-06-14 In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection Diane Kelly Diane Kelly true 0000-0003-2231-0192 false 5ccf81e5d5beedf32ef8d7c3d7ac6c8c 5b3e1902e2bd995f6be76962aa68ddd7 JbnRoDHVq3Anku7dfySsxIJSbZF11mHm1K8NtCGVMYw= 2017-06-14 PMSC 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. Journal article Antimicrobial Agents and Chemotherapy 61 5 e02280-16 0066-4804 1098-6596 0 0 2017 2017-01-01 10.1128/AAC.02280-16 Swansea University Medical School Medicine CMED PMSC Microbes and immunity Doctoral None 2017-07-26T11:19:56Z 2017-06-14T09:36:17Z Swansea University Medical School Medicine Thomas Colley 1 Alexandre Alanio 2 Steven L. Kelly 3 Gurpreet Sehra 4 Yasuo Kizawa 5 Andrew G. S. Warrilow 6 Josie E. Parker 7 Diane E. Kelly 8 Genki Kimura 9 Lauren Anderson-Dring 10 Takahiro Nakaoki 11 Mihiro Sunose 12 Stuart Onions 13 Damien Crepin 14 Franz Lagasse 15 Matthew Crittall 16 Jonathan Shannon 17 Michael Cooke 18 Stéphane Bretagne 19 John King-Underwood 20 John Murray 21 Kazuhiro Ito 22 Pete Strong 23 Garth Rapeport 24 0034336-26072017111739.pdf Antimicrob.AgentsChemother.-2017-Colley-.pdf 2017-07-26T11:17:39Z Output 838409 application/pdf VoR true Updated Notes 26/07/2017 2017-07-26T00:00:00 This is an open access article distributed under the terms of the Creative Commons CC-BY Attribution License. true eng
title In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
spellingShingle In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
Kelly, Diane
title_short In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
title_full In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
title_fullStr In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
title_full_unstemmed In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
title_sort In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
author_id_str_mv 5ccf81e5d5beedf32ef8d7c3d7ac6c8c
author_id_fullname_str_mv 5ccf81e5d5beedf32ef8d7c3d7ac6c8c_***_Kelly, Diane
author Kelly, Diane
author2 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
format Journal article
container_title Antimicrobial Agents and Chemotherapy
container_volume 61
container_issue 5
container_start_page e02280-16
publishDate 2017
institution Swansea University
issn 0066-4804
1098-6596
doi_str_mv 10.1128/AAC.02280-16
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 1
active_str 1
researchgroup_str Microbes and immunity
description 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.
published_date 2017-01-01T11:17:41Z
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score 11.013731

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