Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury

[Image: see text] We previously developed IM-54 as a novel type of inhibitor of hydrogen-peroxide-induced necrotic cell death. Here, we examined its cell death inhibition profile. IM-54 was found to selectively inhibit oxidative stress-induced necrosis, but it did not inhibit apoptosis induced by va...

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Detalles Bibliográficos
Autores principales: Dodo, Kosuke, Shimizu, Tadashi, Sasamori, Jun, Aihara, Kazuyuki, Terayama, Naoki, Nakao, Shuhei, Iuchi, Katsuya, Takahashi, Masahiro, Sodeoka, Mikiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846036/
https://www.ncbi.nlm.nih.gov/pubmed/29541357
http://dx.doi.org/10.1021/acsmedchemlett.7b00454
Descripción
Sumario:[Image: see text] We previously developed IM-54 as a novel type of inhibitor of hydrogen-peroxide-induced necrotic cell death. Here, we examined its cell death inhibition profile. IM-54 was found to selectively inhibit oxidative stress-induced necrosis, but it did not inhibit apoptosis induced by various anticancer drugs or Fas ligand, or necroptosis. IM-17, an IM derivative having improved water-solubility and metabolic stability, was developed and confirmed to retain necrosis-inhibitory activity. IM-17 showed cardioprotective effects in an isolated rat heart model and an in vivo arrhythmia model, suggesting that IM derivatives may have therapeutic potential.

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