title: [Profile of the anti-tumor effects of amrubicin, a completely synthetic anthracycline].
abstract: Amrubicin is a completely synthetic anthracycline derivative. In contrast, however, the anthracyclines used clinically thus far have been produced by fermentation or semisynthesis. Amrubicin is structurally distinguishable from other anthracyclines by the amino group at the 9-position and its unique sugar moiety. Amrubicinol, the C-13 hydroxy- metabolite of amrubicin, is associated with a 5 to 200 times greater cytotoxicity than amrubicin. Amrubicin exhibited superior in vivo antitumor activity to doxorubicin in the human tumor xenograft model. Using this model, the level of amrubicinol (active metabolite) was shown to be higher than that of doxorubicin in tumor tissues, but lower in normal tissues. These results suggest potent therapeutic activity for amrubicin because of the selective distribution of its highly active metabolite, amrubicinol, in tumors. These anti-tumor effects of amrubicin are considered to be induced by DNA topoisomeraseII inhibition. In clinical studies, amrubicin has demonstrated potent single agent activity as compared to a standard regimen in untreated patients with extensive small cell lung cancer. Its major toxicity was myelosuppression (especially neutropenia).
authors.affiliation: Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Hanada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Noguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004273:DNA, Neoplasm / Q000378:metabolism; D003864:Depression, Chemical; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009503:Neutropenia / Q000139:chemically induced; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D059005:Topoisomerase II Inhibitors; C055866:amrubicin