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作者

Tingting Liu Jie Ma Gaopan Dong Mei Zhang Subin Song Xuerui Zhang Shixiang Qi Mingyu Cheng Wenjie Liu Xu Wang Yuqi Gao

作者单位

⁷Department of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA ³School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, China ⁴Department of Breast Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong, 250014, China ²Tingting Liu and Jie Ma contributed equally to this work in the manuscript. ¹Department of Medicinal Chemistry, School of Pharmacy, State Key Laboratory of Advanced Drug Delivery and Release Systems, Shandong First Medical University, Jinan, Shandong, 250117, China ⁶School of Radiology, Shandong First Medical University, Taian, Shandong, 271016, China ⁵Department of Breast Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, Shandong, 250117, China

刊名

European Journal of Medicinal Chemistry

年份

2026

卷号

Vol.301

页码

118180

ISSN

0223-5234

摘要

Eukaryotic elongation factor 2 kinase plays a significant role in tumor cell adaptation under metabolic stress and serves as a promising target for cancer therapy. Nowadays, the research about target protein degradation technology is still in the ascendant, which led to the PROTACs and MGs that induce eEF2K degradation. However, few approaches could realize the real-time monitoring of TPD process, hindering the understanding of protein degradation and the effect it caused. In this study, a ser...更多

Eukaryotic elongation factor 2 kinase plays a significant role in tumor cell adaptation under metabolic stress and serves as a promising target for cancer therapy. Nowadays, the research about target protein degradation technology is still in the ascendant, which led to the PROTACs and MGs that induce eEF2K degradation. However, few approaches could realize the real-time monitoring of TPD process, hindering the understanding of protein degradation and the effect it caused. In this study, a series of novel fluorescence theranostic probes was rationally designed and synthesized, based on an MG targeting eEF2K. As the representative probe, TYMJ-01 exhibited superior degradation efficiency for eEF2K through the ubiquitin–proteasome pathway, as well as outstanding capability of dynamic fluorescence imaging toward intracellular eEF2K degradation in TNBC cells. Furthermore, the probe maintained significant inhibition of cell proliferation, migration, and invasion, and enhanced the antitumor activity of paclitaxel in combination treatment. Therefore, a reliable and efficient toolkit would be provided for eEF2K mechanism study and corresponding drug discovery. Our work could also be beneficial to the study and establishment of TPD and the visualization of a dual-functional system.收起

文献类型

期刊