Journal article 515 views 125 downloads
In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
Antimicrobial Agents and Chemotherapy, Volume: 61, Issue: 5, Start page: e02280-16
-
PDF | Version of Record
This is an open access article distributed under the terms of the Creative Commons CC-BY Attribution License.
Download (845.81KB)
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...
Published in: | Antimicrobial Agents and Chemotherapy |
---|---|
ISSN: | 0066-4804 1098-6596 |
Published: |
2017
|
Online Access: |
Check full text
|
URI: | https://cronfa.swan.ac.uk/Record/cronfa34336 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
first_indexed |
2017-06-14T14:14:54Z |
---|---|
last_indexed |
2018-07-10T10:17:41Z |
id |
cronfa34336 |
recordtype |
SURis |
fullrecord |
<?xml version="1.0"?><rfc1807><datestamp>2017-07-26T11:19:56Z</datestamp><bib-version>v2</bib-version><id>34336</id><entry>2017-06-14</entry><title>In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection</title><alternativeTitle></alternativeTitle><author>Diane Kelly</author><firstname>Diane</firstname><surname>Kelly</surname><active>true</active><ORCID>0000-0003-2231-0192</ORCID><ethesisStudent>false</ethesisStudent><sid>5ccf81e5d5beedf32ef8d7c3d7ac6c8c</sid><email>5b3e1902e2bd995f6be76962aa68ddd7</email><emailaddr>JbnRoDHVq3Anku7dfySsxIJSbZF11mHm1K8NtCGVMYw=</emailaddr><date>2017-06-14</date><deptcode>PMSC</deptcode><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.</abstract><type>Journal article</type><journal>Antimicrobial Agents and Chemotherapy</journal><volume>61</volume><journalNumber>5</journalNumber><paginationStart>e02280-16</paginationStart><paginationEnd/><publisher></publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0066-4804</issnPrint><issnElectronic>1098-6596</issnElectronic><keywords></keywords><publishedDay>0</publishedDay><publishedMonth>0</publishedMonth><publishedYear>2017</publishedYear><publishedDate>2017-01-01</publishedDate><doi>10.1128/AAC.02280-16</doi><url></url><notes></notes><college>Swansea University Medical School</college><department>Medicine</department><CollegeCode>CMED</CollegeCode><DepartmentCode>PMSC</DepartmentCode><institution/><researchGroup>Microbes and immunity</researchGroup><supervisor/><sponsorsfunders/><grantnumber/><degreelevel>Doctoral</degreelevel><degreename>None</degreename><lastEdited>2017-07-26T11:19:56Z</lastEdited><Created>2017-06-14T09:36:17Z</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>Thomas</firstname><surname>Colley</surname><orcid/><order>1</order></author><author><firstname>Alexandre</firstname><surname>Alanio</surname><orcid/><order>2</order></author><author><firstname>Steven L.</firstname><surname>Kelly</surname><orcid/><order>3</order></author><author><firstname>Gurpreet</firstname><surname>Sehra</surname><orcid/><order>4</order></author><author><firstname>Yasuo</firstname><surname>Kizawa</surname><orcid/><order>5</order></author><author><firstname>Andrew G. S.</firstname><surname>Warrilow</surname><orcid/><order>6</order></author><author><firstname>Josie E.</firstname><surname>Parker</surname><orcid/><order>7</order></author><author><firstname>Diane E.</firstname><surname>Kelly</surname><orcid/><order>8</order></author><author><firstname>Genki</firstname><surname>Kimura</surname><orcid/><order>9</order></author><author><firstname>Lauren</firstname><surname>Anderson-Dring</surname><orcid/><order>10</order></author><author><firstname>Takahiro</firstname><surname>Nakaoki</surname><orcid/><order>11</order></author><author><firstname>Mihiro</firstname><surname>Sunose</surname><orcid/><order>12</order></author><author><firstname>Stuart</firstname><surname>Onions</surname><orcid/><order>13</order></author><author><firstname>Damien</firstname><surname>Crepin</surname><orcid/><order>14</order></author><author><firstname>Franz</firstname><surname>Lagasse</surname><orcid/><order>15</order></author><author><firstname>Matthew</firstname><surname>Crittall</surname><orcid/><order>16</order></author><author><firstname>Jonathan</firstname><surname>Shannon</surname><orcid/><order>17</order></author><author><firstname>Michael</firstname><surname>Cooke</surname><orcid/><order>18</order></author><author><firstname>Stéphane</firstname><surname>Bretagne</surname><orcid/><order>19</order></author><author><firstname>John</firstname><surname>King-Underwood</surname><orcid/><order>20</order></author><author><firstname>John</firstname><surname>Murray</surname><orcid/><order>21</order></author><author><firstname>Kazuhiro</firstname><surname>Ito</surname><orcid/><order>22</order></author><author><firstname>Pete</firstname><surname>Strong</surname><orcid/><order>23</order></author><author><firstname>Garth</firstname><surname>Rapeport</surname><orcid/><order>24</order></author></authors><documents><document><filename>0034336-26072017111739.pdf</filename><originalFilename>Antimicrob.AgentsChemother.-2017-Colley-.pdf</originalFilename><uploaded>2017-07-26T11:17:39Z</uploaded><type>Output</type><contentLength>838409</contentLength><contentType>application/pdf</contentType><version>VoR</version><cronfaStatus>true</cronfaStatus><action>Updated Notes</action><actionDate>26/07/2017</actionDate><embargoDate>2017-07-26T00:00:00</embargoDate><documentNotes>This is an open access article distributed under the terms of the Creative Commons CC-BY Attribution License.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents></rfc1807> |
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 |
_version_ |
1605598300578250752 |
score |
11.016258 |