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

doi:10.1021/ml200245t

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

理数教育研究センター

研究成果: Article › 査読

18 被引用数 (Scopus)

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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	English
ページ（範囲）	118-122
ページ数	5
ジャーナル	ACS Medicinal Chemistry Letters
巻	3
号	2
DOI	https://doi.org/10.1021/ml200245t
出版ステータス	Published - 9 2月 2012

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title = "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.",

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T1 - Negamycin analogue with readthrough-promoting activity as a potential drug candidate for Duchenne muscular dystrophy

AU - Taguchi, Akihiro

AU - Nishiguchi, Shigenobu

AU - Shiozuka, Masataka

AU - Nomoto, Takao

AU - Ina, Mayuko

AU - Nojima, Shouta

AU - Matsuda, Ryoichi

AU - Nonomura, Yoshiaki

AU - Kiso, Yoshiaki

AU - Yamazaki, Yuri

AU - Yakushiji, Fumika

AU - Hayashi, Yoshio

PY - 2012/2/9

Y1 - 2012/2/9

N2 - 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.

AB - 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.

KW - Duchenne muscular dystrophy

KW - Negamycin

KW - genetic disease

KW - hydrazino dipeptide

KW - nonsense mutations

KW - readthrough-promoting activity

UR - https://www.scopus.com/pages/publications/84856913604

U2 - 10.1021/ml200245t

DO - 10.1021/ml200245t

M3 - Article

AN - SCOPUS:84856913604

SN - 1948-5875

VL - 3

SP - 118

EP - 122

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 2

ER -

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

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