eEF2K degrader C1 is a small-molecule degrader of eEF2K, acts a molecular glue to enhance the interaction of eEF2K with the ubiquitin E3 ligase βTRCP, thereby promoting the proteasomal degradation of eEF2K.
C1 decreases the level of eEF2K protein in a dose‐dependent manner in TNBC cells, with no significant effect on eEF2K mRNA levels.
MG132, a proteasome inhibitor, blocks the down regulation of eEF2K induced by C1.
C1 enhances the interaction between eEF2K and the ubiquitin E3 ligase βTRCP, MLN4924 remarkedly reverses C1 induced down regulation of eEF2K.
C1 significantly inhibits cell proliferation of MDA‐MB‐231, HCC1806, and BT549 cells with IC50 values of 0.131, 0.342, and 0.262 uM respectively.
C1 treatment (0.4 uM) remarkably inhibits the cell migration and invasion of TNBC cells in wound healing and transwell assays.
C1 shows stronger anti‐cancer activity than paclitaxel, C1 (10 mg/kg) inhibits TNBC growth in mouse xenograft models, also suppresses cell metastasis in the in vivo model.
C1 with paclitaxel synergistically inhibits the growth of TNBC cells in vitro and in vivo.