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

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.
AuthorsAkihiro Taguchi, Shigenobu Nishiguchi, Masataka Shiozuka, Takao Nomoto, Mayuko Ina, Shouta Nojima, Ryoichi Matsuda, Yoshiaki Nonomura, Yoshiaki Kiso, Yuri Yamazaki, Fumika Yakushiji, Yoshio Hayashi
JournalACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 3 Issue 2 Pg. 118-22 (Feb 9 2012) ISSN: 1948-5875 [Electronic] United States
PMID24900441 (Publication Type: Journal Article)

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