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The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer
Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative de...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149907/ https://www.ncbi.nlm.nih.gov/pubmed/37139412 http://dx.doi.org/10.1016/j.apsb.2022.12.019 |
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author | Liu, Yang Xu, Wei Li, Mingxue Yang, Yueying Sun, Dejuan Chen, Lidian Li, Hua Chen, Lixia |
author_facet | Liu, Yang Xu, Wei Li, Mingxue Yang, Yueying Sun, Dejuan Chen, Lidian Li, Hua Chen, Lixia |
author_sort | Liu, Yang |
collection | PubMed |
description | Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers. |
format | Online Article Text |
id | pubmed-10149907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101499072023-05-02 The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer Liu, Yang Xu, Wei Li, Mingxue Yang, Yueying Sun, Dejuan Chen, Lidian Li, Hua Chen, Lixia Acta Pharm Sin B Review Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers. Elsevier 2023-04 2023-02-02 /pmc/articles/PMC10149907/ /pubmed/37139412 http://dx.doi.org/10.1016/j.apsb.2022.12.019 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://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 Liu, Yang Xu, Wei Li, Mingxue Yang, Yueying Sun, Dejuan Chen, Lidian Li, Hua Chen, Lixia The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title | The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title_full | The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title_fullStr | The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title_full_unstemmed | The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title_short | The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
title_sort | regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149907/ https://www.ncbi.nlm.nih.gov/pubmed/37139412 http://dx.doi.org/10.1016/j.apsb.2022.12.019 |
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