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Dual-target inhibitors of poly (ADP-ribose) polymerase-1 for cancer therapy: Advances, challenges, and opportunities.

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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]College of Life Sciences, Sichuan University, Chengdu, 610064, 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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PARP1 plays a crucial role in DNA damage repair, making it an essential target for cancer therapy. PARP1 inhibitors are widely used to treat BRCA-deficient malignancies, and six PARP inhibitors have been approved for clinical use. However, excluding the great clinical success of PARP inhibitors, the concomitant toxicity, drug resistance, and limited scope of application restrict their clinical efficacy. To find solutions to these problems, dual-target inhibitors have shown great potential. In recent years, several studies have linked PAPR1 to other primary cancer targets. Many dual-target inhibitors have been developed using structural fusion, linkage, or library construction methods, overcoming the defects of many single-target inhibitors of PARP1 and achieving great success in clinical cancer therapy. This review summarizes the advance of dual-target PARP1 inhibitors in recent years, focusing on their structural optimization process, structure-activity relationships (SARs), and in vitro or in vivo analysis results.Copyright © 2021 Elsevier Masson SAS. All rights reserved.

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出版当年[2021]版：

大类 | 1 区

医学

小类 | 1 区药物化学

最新[2023]版：

大类 | 2 区

医学

小类 | 1 区药物化学

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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 [4]College of Life Sciences, Sichuan University, Chengdu, 610064, 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 Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

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