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This review integrates regulatory roles in metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, and summarizes available IDH1 inhibitors, including clinical and preclinical 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is IDH1 considered a promising anti-cancer target?","Question",{"text":63,"@type":64},"Pan-cancer research shows IDH1 has a higher mutation frequency and involves more cancer types than IDH2, indicating strong relevance to tumor development and progression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do mutant IDH1/IDH2 contribute to cancer metabolism?",{"text":68,"@type":64},"Mutant IDH1 or IDH2 uses α-ketoglutarate as substrate to produce D-2-hydroxyglutarate (D-2HG), which mediates the occurrence and development of cancer.",{"name":70,"@type":61,"acceptedAnswer":71},"What regulatory aspects does this review cover regarding IDH1 in cancer?",{"text":72,"@type":64},"The review summarizes IDH1 regulatory mechanisms across four areas: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic 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of Materia Medica, Chinese Academy of Medical Sciences  \nActa Pharmaceutica Sinica B  \n[www. elsevier.com/locate/apsb](www. elsevier.com/locate/apsb)[ ](www. elsevier.com/locate/apsb)[www. sciencedirect.com](www. sciencedirect.com)  \nREVIEW  \nThe regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer  \nYang Liua,y, Wei Xuc,y, Mingxue Lia, Yueying Yanga, Dejuan Suna, Lidian Chenb, * , Hua Lia,c, *, Lixia Chena, *  \naWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China  \nbThe Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China cInstitute of Structural Pharmacology & TCM Chemical Biology, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China  \nReceived 23 September 2022; received in revised form 7 November 2022; accepted 18 November 2022  \nKEY WORDS IDH1;  \nCancer;  \nRegulatory mechanisms; IDH1 inhibitors;  \nD-2HG; Metabolic  \nreprogramming; Epigenetics;  \nImmune microenvironment  \nAbstract 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 a-ketoglutarate (a-KG) . Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate (D-2HG) with a-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.  \nª 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \n*Corresponding authors. Tel./fax: þ86 24 23986463.  \nE-mail addresses: [cld@fjtcm.edu.cn](cld@fjtcm.edu.cn) (Lidian Chen), [5402118@qq.com](5402118@qq.com) (Hua Li), [syzyclx@163.com](syzyclx@163.com) (Lixia Chen).  \ny These authors made equal contributions to this work.  \nPeer review under responsibility of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.  \n[https://doi.org/10.1016/j.apsb.2022.12.019](https://doi.org/10.1016/j.apsb.2022.12.019)  \n2211-3835 ª 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \n1. Introduction  \nCancer seriously threatens human life and health. On January 6, 2022, the International Agency for Research on Cancer (IARC) under the World Health Organization released the IARC Biennial Report 2020e2021 . The latest assessment shows that in this century, cancer is expected to overtake","cbCaipVu3TyeNKQ7","https://ap.wps.com/l/cbCaipVu3TyeNKQ7","pdf",4700163,29,"English","# 1. Introduction\n## Cancer risk and hallmarks framework\n## Warburg effect and metabolic reprogramming\n## Hypoxia signaling (HIF-1) and energy regulation","[{\"question\":\"Why is IDH1 considered a promising anti-cancer target?\",\"answer\":\"Pan-cancer research shows IDH1 has a higher mutation frequency and involves more cancer types than IDH2, indicating strong relevance to tumor development and progression.\"},{\"question\":\"How do mutant IDH1/IDH2 contribute to cancer metabolism?\",\"answer\":\"Mutant IDH1 or IDH2 uses α-ketoglutarate as substrate to produce D-2-hydroxyglutarate (D-2HG), which mediates the occurrence and development of cancer.\"},{\"question\":\"What regulatory aspects does this review cover regarding IDH1 in cancer?\",\"answer\":\"The review summarizes IDH1 regulatory mechanisms across four areas: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes.\"}]","The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer - Review | PDF",1790560895,73]