Development of a novel inotropic and lucitorpic agent for treatment of heart failure

开发用于治疗心力衰竭的新型正性肌力药物和促光亮药物

• 批准号: 22390050
• 负责人: INUI Makoto
• 金额: $ 11.73万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390050/
• 关键词: ホスホランバン; アプタマー; 心筋小胞体; 心不全治療薬; カルシウム輸送; 強心薬

We developed a phospholamban specific RNA aptamer as a novel inotropic and lucitropic agent to treat heart failure. The obtained aptamer increased Ca2+ uptake by cardiac sarcoplasmic reticulum in the nanomolar range. To introduce it into cardiomyocytes, we conjugated a membrane penetrating peptide to the aptamer. This aptamer facilitated contraction as well as relaxation of isolated cardiomyocytes. Furthermore, the aptamer improved cardiac functions in vivo. A membrane penetrating peptide-conjugated phospholamban aptamer is thus a potent inotropic and lucitropic agent and could be a novel drug for heart failure.

我们开发了一种受磷蛋白特异性 RNA 适体作为一种新型正性肌力和促亮剂来治疗心力衰竭。获得的适体在纳摩尔范围内增加了心脏肌浆网对Ca2+的吸收。为了将其引入心肌细胞，我们将穿膜肽与适体结合。该适体促进了分离的心肌细胞的收缩和舒张。此外，该适体还改善了体内心脏功能。因此，膜穿透肽缀合的受磷蛋白适体是一种有效的正性肌力和促亮剂，并且可能成为治疗心力衰竭的新药。

项目成果

ホスホランバン標的修飾RNAアプタマー

Phospholamban 靶标修饰 RNA 适体

• 发表时间: 2012

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

• DOI: 10.1152/ajpcell.00343.2012
• 发表时间: 2013-06-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
• 影响因子: 5.5
• 作者: Honda, Takeshi;Ishii, Aiko;Inui, Makoto
• 通讯作者: Inui, Makoto

Concise Synthesis of 2-Benzazepine Derivatives and Their Biological Activity

• DOI: 10.1021/jo300380z
• 发表时间: 2012-04-20
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: So, Masahiro;Kotake, Tomoko;Kamimura, Akio
• 通讯作者: Kamimura, Akio

RNA aptamers against phospholamban with improved stability and efficacy

针对受磷蛋白的 RNA 适体具有更高的稳定性和功效

• 发表时间: 2012
• 作者: Yoshie Tanaka;et al
• 通讯作者: et al

Isoform-specific role of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca^<2+> cycling

蛋白磷酸酶 1 催化亚基在肌浆网介导的 Ca^2 循环中的异构体特异性作用

• 发表时间: 2011
• 期刊: Cardiovascular Research
• 影响因子: 10.8
• 作者: Ueta;Y.;Hidekazu Aoyama
• 通讯作者: Hidekazu Aoyama