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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)118-122
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number2
DOIs
Publication statusPublished - Feb 9 2012

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Dystrophin
Duchenne Muscular Dystrophy
Creatine Kinase
Toxicity
Muscle
Fibers
Pharmaceutical Preparations
Inbred mdx Mouse
Nonsense Codon
Structure-Activity Relationship
Muscles
Serum
negamycin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Negamycin analogue with readthrough-promoting activity as a potential drug candidate for Duchenne muscular dystrophy. / Taguchi, Akihiro; Nishiguchi, Shigenobu; Shiozuka, Masataka; Nomoto, Takao; Ina, Mayuko; Nojima, Shouta; Matsuda, Ryoichi; Nonomura, Yoshiaki; Kiso, Yoshiaki; Yamazaki, Yuri; Yakushiji, Fumika; Hayashi, Yoshio.

In: ACS Medicinal Chemistry Letters, Vol. 3, No. 2, 09.02.2012, p. 118-122.

Research output: Contribution to journalArticle

Taguchi, A, Nishiguchi, S, Shiozuka, M, Nomoto, T, Ina, M, Nojima, S, Matsuda, R, Nonomura, Y, Kiso, Y, Yamazaki, Y, Yakushiji, F & Hayashi, Y 2012, 'Negamycin analogue with readthrough-promoting activity as a potential drug candidate for Duchenne muscular dystrophy', ACS Medicinal Chemistry Letters, vol. 3, no. 2, pp. 118-122. https://doi.org/10.1021/ml200245t
Taguchi, Akihiro ; Nishiguchi, Shigenobu ; Shiozuka, Masataka ; Nomoto, Takao ; Ina, Mayuko ; Nojima, Shouta ; Matsuda, Ryoichi ; Nonomura, Yoshiaki ; Kiso, Yoshiaki ; Yamazaki, Yuri ; Yakushiji, Fumika ; Hayashi, Yoshio. / Negamycin analogue with readthrough-promoting activity as a potential drug candidate for Duchenne muscular dystrophy. In: ACS Medicinal Chemistry Letters. 2012 ; Vol. 3, No. 2. pp. 118-122.
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