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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...

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Autores principales: Liu, Yang, Xu, Wei, Li, Mingxue, Yang, Yueying, Sun, Dejuan, Chen, Lidian, Li, Hua, Chen, Lixia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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