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

摘要

The natural product,BE-43547A2,decreases pancreatic cancer cell sternness.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(eEFlAl).This binding mode was confirmed by a series of experiments including a xenograft mouse model.We also determined that eEFlAl plays an important role in regulating pancreatic cancer cell sternness.Analyses of 99 clinical pancreatic cancer samples revealed that eEFlAl expressions are closely correlated with clinico-pathological grade and patient survival.In conclusion,eEFlAl is involved in pancreatic cancer progression and is therefore,a promising novel covalent target for pancreatic cancer treatment.