{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:50:15Z","timestamp":1791240615573,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"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":[[2002,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            TAK-456 is a novel oral triazole compound with potent and broad-spectrum in vitro antifungal activity and strong in vivo efficacy against\n            <jats:italic>Candida albicans<\/jats:italic>\n            and\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            . TAK-456 inhibited sterol synthesis of\n            <jats:italic>C. albicans<\/jats:italic>\n            and\n            <jats:italic>A. fumigatus<\/jats:italic>\n            by 50% at 3 to 11 ng\/ml. TAK-456 showed strong in vitro activity against clinical isolates of\n            <jats:italic>Candida<\/jats:italic>\n            spp.,\n            <jats:italic>Aspergillus<\/jats:italic>\n            spp., and\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            , except for\n            <jats:italic>Candida glabrata<\/jats:italic>\n            . The MICs at which 90% of the isolates tested were inhibited byTAK-456, fluconazole, itraconazole, voriconazole, and amphotericin B were 0.25, 4, 0.5, 0.13, and 0.5 \u03bcg\/ml, respectively, for clinical isolates of\n            <jats:italic>C. albicans<\/jats:italic>\n            and 1, &gt;64, 0.5, 0.5, and 0.5 \u03bcg\/ml, respectively, for clinical isolates of\n            <jats:italic>A. fumigatus<\/jats:italic>\n            . Therapeutic activities of TAK-456 and reference triazoles against systemic lethal infections caused by\n            <jats:italic>C. albicans<\/jats:italic>\n            and\n            <jats:italic>A. fumigatus<\/jats:italic>\n            in mice were investigated by orally administering drugs once daily for 5 days, and efficacies of the compounds were evaluated by the prolongation of survival. In normal mice, TAK-456 and fluconazole were effective against infection caused by fluconazole-susceptible\n            <jats:italic>C. albicans<\/jats:italic>\n            at a dose of 1 mg\/kg. In transiently neutropenic mice, therapeutic activity of TAK-456 at 1 mg\/kg of body weight against infection with the same strain was stronger than those at 1 mg\/kg of fluconazole. TAK-456 was effective against infections with two strains of fluconazole-resistant\n            <jats:italic>C. albicans<\/jats:italic>\n            at a dose of 10 mg\/kg. TAK-456 also expressed activities similar to or higher than those of itraconazole against the infections caused by two strains of\n            <jats:italic>A. fumigatus<\/jats:italic>\n            in neutropenic mice at a dose of 10 mg\/kg. These results suggest that TAK-456 is a promising candidate for development for the treatment of candidiasis and aspergillosis in humans.\n          <\/jats:p>","DOI":"10.1128\/aac.46.5.1388-1393.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:01Z","timestamp":1027764541000},"page":"1388-1393","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum"],"prefix":"10.1128","volume":"46","author":[{"given":"Noboru","family":"Tsuchimori","sequence":"first","affiliation":[{"name":"Pharmacology Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryogo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Kitamoto","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Asai","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Kitazaki","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Iizawa","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Itoh","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Laboratories I"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Okonogi","sequence":"additional","affiliation":[{"name":"Research Management Department, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199754050-00002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/44.2.151"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1163"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/02681218680000221","volume":"24","year":"1986","unstructured":"Barrett-Bee, K. 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