Fujie A, Iwamoto T, Muramatsu H, Okudaira T, Sato I, Furuta T, Tsurumi Y, Hori Y, Hino M, Hashimoto S, Okuhara M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
J Antibiot (Tokyo). 2000 Sep;53(9):920-7. doi: 10.7164/antibiotics.53.920.
FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.
FR901469是一种水溶性大环脂肽内酯（C71H116N14O23），对1,3-β-葡聚糖合酶具有抑制活性，在体外和体内对白色念珠菌和烟曲霉均表现出抗真菌活性。在微量肉汤稀释试验中，FR901469对白色念珠菌FP633和烟曲霉FP1305的最低抑菌浓度分别为0.63和0.16微克/毫升。在小鼠全身感染模型中，通过皮下注射，FR901469对白色念珠菌和烟曲霉均显示出优异的疗效，半数有效剂量分别为0.32和0.2毫克/千克。在患有实验性肺孢子菌肺炎的裸鼠模型中，该化合物还显示出强大的抗肺孢子菌活性。FR901469对小鼠红细胞的溶血活性比两性霉素B弱约30倍。
