2. Academic Validation
  3. Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells

Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells

  • Eur J Med Chem. 2020 Oct 15;204:112505. doi: 10.1016/j.ejmech.2020.112505.
Yao Liu 1,  Yongqi Zhen 2,  Guan Wang 1,  Gaoxia Yang 1,  Leilei Fu 3,  Bo Liu 4,  Liang Ouyang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, 610041, PR China.
  • 2 School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, PR China.
  • 3 School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, PR China. Electronic address: leilei_fu@163.com.
  • 4 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, 610041, PR China. Electronic address: liubo2400@163.com.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, 610041, PR China. Electronic address: ouyangliang@scu.edu.cn.
PMID: 32717479 DOI: 10.1016/j.ejmech.2020.112505
Abstract

Eukaryotic elongation factor 2 kinase (eEF2K) is a key α-kinase that negatively regulates the extension step of protein synthesis, which consumes most of the energy and Amino acids required for protein synthesis. Studies have found that eEF2K protein is related to the breast Cancer. However, existing inhibitor effect has not achieved the desired effect in Cancer therapy. Proteolysis target chimeric (PROTAC) technology is uses Proteasome to degrade target protein to achieve the purpose of inhibiting tumour cell growth. Here, we reported that the use of PROTAC strategy in combining with star eEF2K inhibitor A484954 and its potential derivatives. Consequently, candidate compound 11l was found to degrade eEF2K and induce Apoptosis in human breast carcinoma MDA-MB-231 cells. Together, these findings demonstrate that our eEF2K-targeting PROTAC small molecule would be a potential new strategy for future breast Cancer therapy.

Keywords

Apoptosis; Breast cancer therapy; Eukaryotic elongation factor 2 kinase; MDA-MB-231 cells; Proteolysis target chimeric.

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