{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:49:04Z","timestamp":1760708944949,"version":"3.37.3"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004324","name":"Astellas Pharma US","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004324","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against\n Aspergillus<\/jats:named-content>\n and\n Candida glabrata<\/jats:named-content>\n . We compared its\n in vitro<\/jats:italic>\n activity against wild-type and azole-resistant\n A. fumigatus<\/jats:named-content>\n and\n A. terreus<\/jats:named-content>\n isolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-type\n A. fumigatus<\/jats:named-content>\n isolates, 24\n A. fumigatus<\/jats:named-content>\n isolates with alterations in CYP51A TR\/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), and\n A. terreus<\/jats:named-content>\n isolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC\n 50<\/jats:sub>\n values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) against\n A. fumigatus<\/jats:named-content>\n CYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistant\n A. fumigatus<\/jats:named-content>\n isolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active against\n A. terreus<\/jats:named-content>\n CYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayed\n in vitro<\/jats:italic>\n activity against\n A. fumigatus<\/jats:named-content>\n and\n A. terreus<\/jats:named-content>\n isolates which was independent of the presence or absence of azole target gene resistance mutations in\n A. fumigatus<\/jats:named-content>\n . The findings are promising at a time when azole-resistant\n A. fumigatus<\/jats:named-content>\n is emerging globally.\n <\/jats:p>","DOI":"10.1128\/aac.02336-15","type":"journal-article","created":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T04:09:28Z","timestamp":1447128568000},"page":"532-536","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["In Vitro<\/i>\n Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms"],"prefix":"10.1128","volume":"60","author":[{"given":"Maiken Cavling","family":"Arendrup","sequence":"first","affiliation":[{"name":"Unit for Mycology, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus Hare","family":"Jensen","sequence":"additional","affiliation":[{"name":"Unit for Mycology, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Cuenca-Estrella","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020191"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/510592"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/509917"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/592255"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02832.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/652768"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03548.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu911"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02855-14"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku566"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1710.110226"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit320"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku259"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00185-11"},{"key":"e_1_3_3_17_2","volume-title":"Abstr Intersci Conf Antimicrob Agents Chemother (ICAAC)","author":"Nakamura I","year":"2014","unstructured":"Nakamura I, Ohsumi K, Yoshikawa K, Kanasaki R, Masaki T, Takase S, Hashimoto M, Fujie A, Nakai T, Matsumoto S, Takeda S, Akamatsu S, Uchida S, Maki K. 2014. ASP2397: a novel natural product with potent fungicidal activity against Aspergillus spp. (1)\u2014a new mode of action and in vitro activity, abstr F1590. Abstr Intersci Conf Antimicrob Agents Chemother (ICAAC)."},{"key":"e_1_3_3_18_2","article-title":"EUCAST definitive document E. Def 9.2 method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds","author":"Arendrup MC","year":"2014","unstructured":"Arendrup MC, Hope W, Howard SJ. 2014. EUCAST definitive document E. Def 9.2 method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. EUCAST.","journal-title":"EUCAST"},{"key":"e_1_3_3_19_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard\u20142nd ed","author":"CLSI","year":"2008","unstructured":"CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard\u20142nd ed. CLSI document M38-A2. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01111-13"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00636-13"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02336-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02336-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:34:20Z","timestamp":1645475660000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02336-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1128\/AAC.02336-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02336-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2016,1]]},"assertion":[{"value":"2015-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}