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Pro-senescence neddylation inhibitor combined with a senescence activated β-galactosidase prodrug to selectively target cancer cells.

作者信息

Ni Shuaishuai, Liu Qian, Chen Xin, Ding Lele, Cai Lili, Mao Fei, Shi Donglei, Hoffman Robert M, Li Jian, Jia Lijun

机构信息

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, China.

State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 200037, Shanghai, China.

出版信息

Signal Transduct Target Ther. 2022 Sep 9;7(1):313. doi: 10.1038/s41392-022-01128-2.

DOI:10.1038/s41392-022-01128-2
PMID:36075909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9458665/
Abstract
摘要

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Pro-senescence neddylation inhibitor combined with a senescence activated β-galactosidase prodrug to selectively target cancer cells.促衰老的NEDDylation抑制剂与衰老激活的β-半乳糖苷酶前药联合使用，以选择性地靶向癌细胞。
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Targeting protein neddylation with an NEDD8-activating enzyme inhibitor MLN4924 induced apoptosis or senescence in human lymphoma cells.使用NEDD8激活酶抑制剂MLN4924靶向蛋白质NEDD化可诱导人淋巴瘤细胞凋亡或衰老。
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Overactivated neddylation pathway as a therapeutic target in lung cancer.过度激活的 neddylation 通路作为肺癌的治疗靶点。
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Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice.β-半乳糖苷酶靶向前药消除衰老细胞可减轻老年小鼠的炎症并恢复其身体功能。
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NEDD8-mediated neddylation is required for human endometrial stromal proliferation and decidualization.人子宫内膜基质增殖和蜕膜化需要NEDD8介导的NEDD化。
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Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer.验证 NEDD8 连接酶 UBC12 作为肺癌的一个新治疗靶点。
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The first generation of β-galactosidase-responsive prodrugs designed for the selective treatment of solid tumors in prodrug monotherapy.第一代 β-半乳糖苷酶响应型前药，旨在用于前药单药治疗实体瘤的选择性治疗。
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本文引用的文献

1
Exploiting senescence for the treatment of cancer.利用衰老治疗癌症。
Nat Rev Cancer. 2022 Jun;22(6):340-355. doi: 10.1038/s41568-022-00450-9. Epub 2022 Mar 3.
2
Two-Step Senescence-Focused Cancer Therapies.两步衰老聚焦癌症疗法。
Trends Cell Biol. 2018 Sep;28(9):723-737. doi: 10.1016/j.tcb.2018.04.006. Epub 2018 May 17.
3
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse.细胞衰老促进化疗的不良影响和癌症复发。
K128 泛素化通过扩大其与 GAP 蛋白的结合界面来限制 RAS 的活性。
EMBO J. 2024 Jul;43(14):2862-2877. doi: 10.1038/s44318-024-00146-w. Epub 2024 Jun 10.
4
Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs.半乳糖修饰的 PROTAC 通过选择性消除衰老的癌细胞。
J Med Chem. 2024 May 9;67(9):7301-7311. doi: 10.1021/acs.jmedchem.4c00152. Epub 2024 Apr 18.
5
Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.靶向衰老和与年龄相关疾病中的细胞衰老：挑战、考虑因素以及衰老溶解和衰老模拟疗法的新兴作用。
Aging Dis. 2024 Feb 27;15(6):2554-2594. doi: 10.14336/AD.2024.0206.
6
Senolysis Enabled by Senescent Cell-Sensitive Bioorthogonal Tetrazine Ligation.衰老细胞敏感的生物正交四嗪连接促进衰老细胞消除。
Angew Chem Int Ed Engl. 2024 Feb 26;63(9):e202315425. doi: 10.1002/anie.202315425. Epub 2024 Jan 30.
7
Discovery of neddylation E2s inhibitors with therapeutic activity.具有治疗活性的NEDDylation E2s抑制剂的发现。
Oncogenesis. 2023 Sep 16;12(1):45. doi: 10.1038/s41389-023-00490-2.
Cancer Discov. 2017 Feb;7(2):165-176. doi: 10.1158/2159-8290.CD-16-0241. Epub 2016 Dec 15.
4
Overactivated neddylation pathway as a therapeutic target in lung cancer.过度激活的 neddylation 通路作为肺癌的治疗靶点。
J Natl Cancer Inst. 2014 May 22;106(6):dju083. doi: 10.1093/jnci/dju083. Print 2014 Jun.
5
Induction of p21-dependent senescence by an NAE inhibitor, MLN4924, as a mechanism of growth suppression.NAE 抑制剂 MLN4924 通过诱导 p21 依赖性衰老来抑制细胞生长的机制研究。
Neoplasia. 2011 Jun;13(6):561-9. doi: 10.1593/neo.11420.