SM 5887

small and small-cell lung cancers. Amrubicin, a completely synthetic anthracycline derivative, mediates its growth inhibitory action via topoisomerase II inhibition. It is activated in viva by the formation of its 13-OH metabolite, amrubicinol, via reaction with carbonyl reductase. In contrast to doxorubicin and daunorubicin whose metabolites are inactive in the blood, amrubicinol is 10-100 fold more cytotoxic than amrubicin. In phase II clinical trials, amrubicin showed antitumor activity against non-small-cell lung cancers (response rate exceeding 20%) and against untreated extensive stage small-cell-lung cancers (response rate 78.8%). Amrubicin demonstrated a smaller distribution-volume, a shorter half-life in mice and also less chronic cardiotoxicity in preclinical studies compared to doxorubicin. Amrubicin was generally well tolerated with major adverse events being anaemia, leucopenia, thrombocytopenia and neutropenia.

Sumitomo (Japan)

Amrubicin (SM-5887) hydrochloride is a DNA topoisomerase II inhibitor, used for the research of cancer.

Calsed

Topoisomerase II

[1] Hayashi S, et al. Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction. Int J Mol Med. 2006 Nov;18(5):909-15. PMID:17016621
[2] Hanada M, et al. Amrubicin, a novel 9-aminoanthracycline, enhances the antitumor activity of chemotherapeutic agents against human cancer cells in vitro and in vivo. Cancer Sci. 2007 Mar;98(3):447-54. DOI:10.1111/j.1349-7006.2007.00404.x
[3] Hanada M, et al. Amrubicin induces apoptosis in human tumor cells mediated by the activation of caspase-3/7 preceding a loss of mitochondrial membrane potential. Cancer Sci. 2006 Dec;97(12):1396-403. Epub 2006 Sep 21. DOI:10.1111/j.1349-7006.2006.00318.x