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Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives

Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, bu...

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Detalles Bibliográficos
Autores principales: Yin, Yizhen, Chen, Fener
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745060/
https://www.ncbi.nlm.nih.gov/pubmed/33354500
http://dx.doi.org/10.1016/j.apsb.2020.02.012
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author Yin, Yizhen
Chen, Fener
author_facet Yin, Yizhen
Chen, Fener
author_sort Yin, Yizhen
collection PubMed
description Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, but not required for the proliferation of normal cells. Therefore, dozens of MTH1 inhibitors have been developed with the aim of suppressing cancer growth by accumulating oxidative damage in cancer cells. While several inhibitors were indeed confirmed to be effective, some inhibitors failed to kill cancer cells, complicating MTH1 as a viable target for cancer eradication. In this review, we summarize the current status of developing MTH1 inhibitors as drug candidates, classify the MTH1 inhibitors based on their structures, and offer our perspectives toward the therapeutic potential against cancer through the targeting of MTH1.
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spelling pubmed-77450602020-12-21 Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives Yin, Yizhen Chen, Fener Acta Pharm Sin B Review Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, but not required for the proliferation of normal cells. Therefore, dozens of MTH1 inhibitors have been developed with the aim of suppressing cancer growth by accumulating oxidative damage in cancer cells. While several inhibitors were indeed confirmed to be effective, some inhibitors failed to kill cancer cells, complicating MTH1 as a viable target for cancer eradication. In this review, we summarize the current status of developing MTH1 inhibitors as drug candidates, classify the MTH1 inhibitors based on their structures, and offer our perspectives toward the therapeutic potential against cancer through the targeting of MTH1. Elsevier 2020-12 2020-03-30 /pmc/articles/PMC7745060/ /pubmed/33354500 http://dx.doi.org/10.1016/j.apsb.2020.02.012 Text en © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Yin, Yizhen
Chen, Fener
Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title_full Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title_fullStr Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title_full_unstemmed Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title_short Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
title_sort targeting human mutt homolog 1 (mth1) for cancer eradication: current progress and perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745060/
https://www.ncbi.nlm.nih.gov/pubmed/33354500
http://dx.doi.org/10.1016/j.apsb.2020.02.012
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