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The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Acta Pharmaceutica Sinica B 2023年第4期13卷 1438-1466页

作者： Yang Liu Wei Xu Mingxue Li Yueying Yang dejuan Sun Lidian Chen Hua Li Lixia Chen Wuya College of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China The Institute of Rehabilitation Industry Fujian University of Traditional Chinese MedicineFuzhou 350122China Institute of Structural Pharmacology&TCM Chemical Biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment *** 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 *** present,no IdH3 mutation has been *** 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 ***,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 *** addition,we also reviewed available IdH1 inhibitors so *** 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.

关键词： IdH1 Cancer Regulatory mechanisms IdH1 inhibitors d-2hg Metabolic reprogramming Epigenetics Immune microenvironment

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