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
复制标题
设计诱导 MDA-MB-231 细胞凋亡的 eEF2K 靶向 PROTAC 小分子
DOI：
10.1016/j.ejmech.2020.112505
复制
发表时间：
2020-10-15
影响因子：
6.7
通讯作者：
Ouyang, Liang
中科院分区：
文献类型：
--
作者：
Liu, Yao;Zhen, Yongqi;Ouyang, Liang
Eukaryotic elongation factor 2 kinase (eEF2K) is a key alpha-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. (C) 2020 Elsevier Masson SAS. All rights reserved.
