{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:29:46Z","timestamp":1768883386814,"version":"3.49.0"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[1995,5,1]],"date-time":"1995-05-01T00:00:00Z","timestamp":799286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1995,5]]},"abstract":"<jats:p>The activities of the water-soluble pneumocandin derivatives L-733560, L-705589, and L-731373 were evaluated in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis and were compared with those of commercially available antifungal agents. Pneumocandins are inhibitors of 1,3-beta-D-glucan synthesis. In the aspergillosis model, L-733560 and L-705589 significantly prolonged the survival of DBA\/2N mice challenged intravenously with Aspergillus fumigatus conidia. L-733560 and L-705589 exhibited efficacies comparable to that of amphotericin B (AMB) with 90% effective doses of 0.48, 0.12, and 0.36 mg\/kg of body weight, respectively. Two mouse models of disseminated candidiasis were used to evaluate these compounds. In both models, mice were challenged intravenously with Candida albicans. In a C. albicans survival model with DBA\/2N and CD-1 mice, the efficacy of L-733560 was comparable to that of AMB, while L-731373 and L-705589 were somewhat less active. In a previously described C. albicans target organ kidney assay, the pneumocandin analogs and AMB at doses of &gt; or = 0.09 mg\/kg were effective in sterilizing kidneys, while fluconazole and ketoconazole were considerably less active and did not sterilize kidneys when they were used at concentrations of &lt; or = 100 mg\/kg. Although orally administered L-733560 showed activity in both candidiasis models, its efficacy was reduced compared with that of parenterally administered drug. In a disseminated cryptococcosis mouse model that measures the number of CFU of Cryptococcus neoformans per gram of brain and spleen, L-733560 at 10 mg\/kg was ineffective in reducing the counts in organs, while AMB at 0.31 mg\/kg sterilized the organs. These results indicate that the pneumocandins may be beneficial as potent parenterally administered therapeutic agents for disseminated aspergillosis and candidiasis.<\/jats:p>","DOI":"10.1128\/aac.39.5.1077","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:06:25Z","timestamp":1340841985000},"page":"1077-1081","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, and L-731373 with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis"],"prefix":"10.1128","volume":"39","author":[{"given":"G K","family":"Abruzzo","sequence":"first","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A M","family":"Flattery","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C J","family":"Gill","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Kong","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J G","family":"Smith","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Krupa","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V B","family":"Pikounis","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kropp","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Bartizal","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.5.1077","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.5.1077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T19:59:56Z","timestamp":1645473596000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.39.5.1077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995,5]]}},"alternative-id":["10.1128\/AAC.39.5.1077"],"URL":"https:\/\/doi.org\/10.1128\/aac.39.5.1077","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,5]]},"assertion":[{"value":"1995-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}