2. Academic Validation
  3. Establishment of environment-sensitive probes targeting BRD3/BRD4 for imaging and therapy of tumor

Establishment of environment-sensitive probes targeting BRD3/BRD4 for imaging and therapy of tumor

  • Eur J Med Chem. 2023 Sep 5;257:115478. doi: 10.1016/j.ejmech.2023.115478.
Yuqi Gao 1,  Jie Zhang 2,  JianJun Li 2,  Shubin Song 3,  Sitao Zhang 2,  Qiao Liu 2,  Xu Wang 4,  Jinbo Zhao 2,  Chengcai Xia 2,  Yuliang Xiao 5,  Tingting Liu 6
Affiliations

Affiliations

  • 1 College of Radiology, Shandong First Medical University, University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, China; Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, Shandong, 250117, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
  • 3 Department of Breast Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
  • 4 Department of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 5 Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: xiaoyl@sdfmu.edu.cn.
  • 6 Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: liutingting@sdfmu.edu.cn.
PMID: 37269669 DOI: 10.1016/j.ejmech.2023.115478
Abstract

The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as Cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a-6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of Apoptosis. All these features render 6a may compatible for immunofluorescent studies and future Cancer diagnosis, and guide for the discovery of new Anticancer drugs.

Keywords

BRD3/BRD4 proteins; Cells and tissues; Fluorescent probes; Imaging.

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