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Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor

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Abstract

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

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Authors and Affiliations

  1. Shionogi Research Laboratories, Shionogi & Co., Ltd, Fukushima-ku, Osaka, Japan

    Ryuji Maekawa, Hideo Maki, Tohru Wada, Hiroshi Yoshida, Kazuyo Nishida-Nishimoto, Hiroyuki Okamoto, Yayoi Matsumoto, Hiroshige Tsuzuki & Takayuki Yoshioka

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  1. Ryuji Maekawa
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  2. Hideo Maki
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  3. Tohru Wada
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  4. Hiroshi Yoshida
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  5. Kazuyo Nishida-Nishimoto
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  6. Hiroyuki Okamoto
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  7. Yayoi Matsumoto
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  8. Hiroshige Tsuzuki
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  9. Takayuki Yoshioka
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Maekawa, R., Maki, H., Wada, T. et al. Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor. Clin Exp Metastasis 18, 61–66 (2000). https://doi.org/10.1023/A:1026553414492

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