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Recent advances of human dihydroorotate dehydrogenase inhibitors for cancer therapy: Current development and future perspectives.

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机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, 38163, Tennessee, United States [4]Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu, Sichuan, 611130, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

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Human dihydroorotate dehydrogenase (hDHODH) is a flavin-dependent enzyme catalyzing the fourth step of pyrimidine de novo biosynthesis. Since aberrant pyrimidine metabolism is closely related abnormal cell proliferation, hDHODH is believed to have an intimate linkage with cancers. For instance, hDHODH induces the abrogation of β-catenin degradation and cell proliferation in esophageal squamous cell carcinoma (ESCC). Thus, small molecular inhibitors targeting hDHODH has been considered as a promising strategy for cancer treatment. In recent years, in exploiting novel structural hDHODH inhibitors (hDHODHi), a candidate drug PTC299 has entered clinical trials for treating acute myelocytic leukemia (AML) and other tumors. This review discusses tumor-related research of hDHODH and highlights the structure-activity relationships of hDHODHi, providing insights into new drugs targeting hDHODH for antitumor clinical practice.Copyright © 2022 Elsevier Masson SAS. All rights reserved.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区药物化学

最新[2025]版：

大类 | 2 区医学

小类 | 1 区药物化学

第一作者：

第一作者机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

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通讯作者：

通讯机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [*1]Targeted Tracer Research and Development Laboratory,Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National ClinicalResearch Center for Geriatrics, West China Hospital, Sichuan University, Chengdu,610041, Sichuan, China.

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