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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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522005287 |
| _version_ | 1827964219717320704 |
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| author | Yang Liu Wei Xu Mingxue Li Yueying Yang Dejuan Sun Lidian Chen Hua Li Lixia Chen |
| author_facet | Yang Liu Wei Xu Mingxue Li Yueying Yang Dejuan Sun Lidian Chen Hua Li Lixia Chen |
| author_sort | Yang Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T17:12:12Z |
| format | Article |
| id | doaj.art-179b82c81ad949808cea6e2044e7e704 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-09T17:12:12Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-179b82c81ad949808cea6e2044e7e7042023-04-20T04:36:26ZengElsevierActa Pharmaceutica Sinica B2211-38352023-04-0113414381466The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancerYang Liu0Wei Xu1Mingxue Li2Yueying Yang3Dejuan Sun4Lidian Chen5Hua Li6Lixia Chen7Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaInstitute of Structural Pharmacology & TCM Chemical Biology, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaThe Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Corresponding authors. Tel./fax: +86 24 23986463.Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Institute of Structural Pharmacology & TCM Chemical Biology, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Corresponding authors. Tel./fax: +86 24 23986463.Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors. Tel./fax: +86 24 23986463.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.http://www.sciencedirect.com/science/article/pii/S2211383522005287IDH1CancerRegulatory mechanismsIDH1 inhibitorsD-2HGMetabolic reprogramming |
| spellingShingle | Yang Liu Wei Xu Mingxue Li Yueying Yang Dejuan Sun Lidian Chen Hua Li Lixia Chen The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer Acta Pharmaceutica Sinica B IDH1 Cancer Regulatory mechanisms IDH1 inhibitors D-2HG Metabolic reprogramming |
| 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 | IDH1 Cancer Regulatory mechanisms IDH1 inhibitors D-2HG Metabolic reprogramming |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522005287 |
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