Lack of Mutagenicity of SMD-502, a New Vitamin D₃ Analog for Topical Application, in Skin and Liver of gpt delta Transgenic Mice and in GDL1 Cells

DOI Web Site 参考文献21件
  • Takeiri Akira
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Tanaka Kenji
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Shioda Akifumi
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Harada Asako
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Yano Mariko
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Kawase Akira
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Yamaguchi Koji
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Mitsui Tetsuya
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
  • Mishima Masayuki
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.

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タイトル別名
  • Lack of Mutagenicity of SMD-502, a New Vitamin D<sub>3</sub> Analog for Topical Application, in Skin and Liver of <i>gpt</i> delta Transgenic Mice and in GDL1 Cells

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説明

SMD-502, a new vitamin D3 (VD3) analog, is an antipsoriatic drug candidate. The compound exhibited fewer side effects than known VD3 analogs in animal models, probably because the compound is rapidly converted into pharmacologically inactive form after permeating into systemic circulation from the application site on skin. This feature of the compound makes it difficult to assess genotoxic risk in vivo with the standard approach of bone marrow or peripheral blood micronucleus assays in rodents because of the low blood concentration level. To evaluate in vivo mutagenicity of the compound in the present study, mutant frequency (MF) in skin and liver of gpt delta transgenic mice was examined with percutaneous administration of SMD-502 for 28 days. In tissues collected 7 days after the end of administration, no significant increase in the MF was observed in either skin or liver. Additionally, when the compound was tested in a GDL1 cell line established from gpt delta mice, GDL1 cells exhibited no significant increase in MFs even under conditions in which they would be exposed to a much higher concentration of the compound than in the in vivo study. The results in this study further supported the consideration that SMD-502 has no mutagenic activity.<br>

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