{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:48:20Z","timestamp":1791557300028,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pulmocide Ltd.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Disease due to pulmonary Aspergillus infection remains a significant unmet need, particularly in immunocompromised patients, patients in critical care and those with underlying chronic lung diseases. To date, treatment using inhaled antifungal agents has been limited to repurposing available systemic medicines. PC945 is a novel triazole antifungal agent, a potent inhibitor of CYP51, purpose-designed to be administered via inhalation for high local lung concentrations and limited systemic exposure. In preclinical testing, PC945 is potent versus Aspergillus spp. and Candida spp. and showed two remarkable properties in preclinical studies, in vitro and in vivo. The antifungal effects against Aspergillus fumigatus accumulate on repeat dosing and improved efficacy has been demonstrated when PC945 is dosed in combination with systemic anti-fungal agents of multiple classes. Resistance to PC945 has been induced in Aspergillus fumigatus in vitro, resulting in a strain which remained susceptible to other antifungal triazoles. In healthy volunteers and asthmatics, nebulised PC945 was well tolerated, with limited systemic exposure and an apparently long lung residency time. In two lung transplant patients, PC945 treated an invasive pulmonary Aspergillus infection that had been unresponsive to multiple antifungal agents (systemic \u00b1 inhaled) without systemic side effects or detected drug\u2013drug interactions.<\/jats:p>","DOI":"10.3390\/jof6040373","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections"],"prefix":"10.3390","volume":"6","author":[{"given":"Alison","family":"Murray","sequence":"first","affiliation":[{"name":"Pulmocide Ltd., Office Suite 3.01, 44 Southampton Buildings, London WC2A 1AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3719-0883","authenticated-orcid":false,"given":"Lindsey","family":"Cass","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd., Office Suite 3.01, 44 Southampton Buildings, London WC2A 1AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-2717","authenticated-orcid":false,"given":"Kazuhiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd., Office Suite 3.01, 44 Southampton Buildings, London WC2A 1AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Pagani","sequence":"additional","affiliation":[{"name":"Royal Brompton and Harefield NHS Foundation Trust, Respiratory and Transplant Medicine, Harefield Hospital, Harefield UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Armstrong-James","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paras","family":"Dalal","sequence":"additional","affiliation":[{"name":"Royal Brompton and Harefield NHS Foundation Trust, Respiratory and Transplant Medicine, Harefield Hospital, Harefield UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Reed","sequence":"additional","affiliation":[{"name":"Royal Brompton and Harefield NHS Foundation Trust, Respiratory and Transplant Medicine, Harefield Hospital, Harefield UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete","family":"Strong","sequence":"additional","affiliation":[{"name":"Pulmocide Ltd., Office Suite 3.01, 44 Southampton Buildings, London WC2A 1AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/ina.12020","article-title":"Isolation of Aspergillus fumigatus from sputum is associated with elevated airborne levels in homes of patients with asthma","volume":"23","author":"Fairs","year":"2013","journal-title":"Indoor Air"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/mmy\/myw121","article-title":"Aspergillus-related pulmonary diseases in lung transplantation","volume":"55","author":"Pasupneti","year":"2017","journal-title":"Med. 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