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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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
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author Dodo, Kosuke
Shimizu, Tadashi
Sasamori, Jun
Aihara, Kazuyuki
Terayama, Naoki
Nakao, Shuhei
Iuchi, Katsuya
Takahashi, Masahiro
Sodeoka, Mikiko
author_facet Dodo, Kosuke
Shimizu, Tadashi
Sasamori, Jun
Aihara, Kazuyuki
Terayama, Naoki
Nakao, Shuhei
Iuchi, Katsuya
Takahashi, Masahiro
Sodeoka, Mikiko
author_sort Dodo, Kosuke
collection PubMed
description [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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spelling pubmed-58460362018-03-14 Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury Dodo, Kosuke Shimizu, Tadashi Sasamori, Jun Aihara, Kazuyuki Terayama, Naoki Nakao, Shuhei Iuchi, Katsuya Takahashi, Masahiro Sodeoka, Mikiko ACS Med Chem Lett [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. American Chemical Society 2018-01-29 /pmc/articles/PMC5846036/ /pubmed/29541357 http://dx.doi.org/10.1021/acsmedchemlett.7b00454 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Dodo, Kosuke
Shimizu, Tadashi
Sasamori, Jun
Aihara, Kazuyuki
Terayama, Naoki
Nakao, Shuhei
Iuchi, Katsuya
Takahashi, Masahiro
Sodeoka, Mikiko
Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title_full Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title_fullStr Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title_full_unstemmed Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title_short Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury
title_sort indolylmaleimide derivative im-17 shows cardioprotective effects in ischemia-reperfusion injury
url 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
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