Probe Synthesis Reveals Eukaryotic Translation Elongation Factor 1 Alpha 1 as the Anti-Pancreatic Cancer Target of BE-43547A2

Can Liu, Liang Wang*, Yuanjun Sun, Xiuhe Zhao, Tianyang Chen, Xiuwen Su, Hui Guo, Qin Wang, Xiaonan Xi, Yahui Ding*, Yue Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The natural product, BE-43547A2, decreases pancreatic cancer cell stemness. However, its anticancer molecular mechanisms have not been fully established. Based on structure–activity relationships of BE-43547A2, we synthesized a probe and investigated its potential targets using an in situ click reaction. We found that BE-43547A2 exerts its anticancer effects by covalently binding the cysteine234 (C234) residue of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). This binding mode was confirmed by a series of experiments including a xenograft mouse model. We also determined that eEF1A1 plays an important role in regulating pancreatic cancer cell stemness. Analyses of 99 clinical pancreatic cancer samples revealed that eEF1A1 expressions are closely correlated with clinicopathological grade and patient survival. In conclusion, eEF1A1 is involved in pancreatic cancer progression and is therefore, a promising novel covalent target for pancreatic cancer treatment.

Original languageEnglish
JournalAngewandte Chemie - International Edition
DOIs
Publication statusAccepted/In press - 2022
Externally publishedYes

Keywords

  • Anticancer Target
  • BE-43547
  • Pancreatic Cancer
  • Target Identification
  • eEF1A

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