Negamycin analogue with readthrough-promoting activity as a potential drug candidate for Duchenne muscular dystrophy

Akihiro Taguchi, Shigenobu Nishiguchi, Masataka Shiozuka, Takao Nomoto, Mayuko Ina, Shouta Nojima, Ryoichi Matsuda, Yoshiaki Nonomura, Yoshiaki Kiso, Yuri Yamazaki, Fumika Yakushiji, Yoshio Hayashi

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)

抄録

A series of (+)-negamycin 1 analogues were synthesized, and their readthrough-promoting activity was evaluated for nonsense mutations in Duchenne muscular dystrophy (DMD). A structure-activity relationship study indicated that 11b was the most potent drug candidate. Immunohistochemical analyses suggested that treatment with 11b restored dystrophin expression in mdx mice, a DMD mouse model. Furthermore, 11b decreased serum creatine kinase (CK) levels, an indicator of muscle fiber destruction. Most importantly, 11b demonstrated lower toxicity than 1, and thus, it could be a useful candidate for long-term treatment of DMD.

本文言語英語
ページ(範囲)118-122
ページ数5
ジャーナルACS Medicinal Chemistry Letters
3
2
DOI
出版ステータス出版済み - 2月 9 2012
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 創薬
  • 有機化学

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