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Development of novel cytoprotective small compounds inhibiting mitochondria-dependent apoptosis
Development of novel cytoprotective small compounds inhibiting mitochondria-dependent apoptosis
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Length:
20 minutes
Released:
Oct 12, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.10.12.511987v1?rss=1
Authors: Matsuyama, S., Matsuyama, M., Ortega, J., Fedorov, Y., Scott-McKean, J., Muller-Greven, J., Buck, M., Adams, D., Jastrzebska, B., Greenlee, W.
Abstract:
We identified cyto-protective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in ocular disease mouse models. M109S directly interacted with Bax and inhibited the conformational change and mitochondrial translocation of Bax. M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only mouse embryonic fibroblasts. M109S also inhibited apoptosis induced by staurosporine, etoposide, and obatoclax. M109S decreased maximal mitochondrial oxygen consumption rate and reactive oxygen species production whereas it increased glycolysis. These effects on cellular metabolism may contribute to the cytoprotective activity of M109S. M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S has the potential to become a new research tool for cell death mechanisms and to develop therapeutics targeting mitochondria-dependent cell death pathway. (146 words)
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http://biorxiv.org/cgi/content/short/2022.10.12.511987v1?rss=1
Authors: Matsuyama, S., Matsuyama, M., Ortega, J., Fedorov, Y., Scott-McKean, J., Muller-Greven, J., Buck, M., Adams, D., Jastrzebska, B., Greenlee, W.
Abstract:
We identified cyto-protective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in ocular disease mouse models. M109S directly interacted with Bax and inhibited the conformational change and mitochondrial translocation of Bax. M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only mouse embryonic fibroblasts. M109S also inhibited apoptosis induced by staurosporine, etoposide, and obatoclax. M109S decreased maximal mitochondrial oxygen consumption rate and reactive oxygen species production whereas it increased glycolysis. These effects on cellular metabolism may contribute to the cytoprotective activity of M109S. M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S has the potential to become a new research tool for cell death mechanisms and to develop therapeutics targeting mitochondria-dependent cell death pathway. (146 words)
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Oct 12, 2022
Format:
Podcast episode
Titles in the series (100)
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