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Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(γ-l-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo

  • Original Articles
  • Antitumor Activity, Mytomycin Derivative, Preclinical, Mitomycin C-Resistant Tumor
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Summary

The antitumor activity of a mitomycin derivative, 7-N-[2-[[2-(γ-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), was evaluated in murine and human tumor models, including a mitomycin C (MMC)-resistant tumor in vitro and in vivo. KW-2149 showed a profound effect against i.p. inoculated P388 leukemia on both a single and an intermittent administration schedule. Against s.c. implanted colon adenocarcinoma 38 (colon 38), KW-2149 was as effective as MMC in ILS% and in tumor growth inhibition on a single-administration schedule. Both compounds were similarly effective when an intermittent schedule was used. KW-2149 showed activity against human tumor xenografts and was effective in two of four non-small-cell lung carcinomas but was not effective against three gastric adenocarcinomas on the singleadministration regimen. The activity of KW-2149 against gastric adenocarcinoma was inferior to that of MMC on a single-administration schedule. However, the antitumor activity of KW-2149 was higher on an intermittent schedule than on a single-administration regimen. The antitumor activity of KW-2149 against human tumor xenografts was similar to that of MMC on an intermittent schedule, and the former drug was effective against both gastric adenocarcinomas and both non-small-cell lung carcinomas. KW-2149 was more effective than MMC against a subline of P388 leukemia that is resistant to MMC in vitro as well as in vivo.

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Authors and Affiliations

  1. Institute of Applied Microbiology, The University of Tokyo, Tokyo, Japan

    Takashi Tsuruo

  2. Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan

    Makoto Morimoto

  3. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Toshima-ku, 170, Tokyo, Japan

    Takashi Tsuruo, Yojiro Sudo, Noriko Asami & Makoto Inaba

Authors
  1. Takashi Tsuruo
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  2. Yojiro Sudo
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  3. Noriko Asami
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  4. Makoto Inaba
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  5. Makoto Morimoto
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Tsuruo, T., Sudo, Y., Asami, N. et al. Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(γ-l-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo. Cancer Chemother. Pharmacol. 27, 89–93 (1990). https://doi.org/10.1007/BF00689089

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  • DOI: https://doi.org/10.1007/BF00689089

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