PROTAC MNK1 degrader-1

Description

PROTAC MNK1 degrader-1 is a selective MNK1 PROTAC degrader with a DC50 of 11.92 nM, and a Dmax > 96 % in MV4-11 cells. PROTAC MNK1 degrader-1 significantly reduces p-eIF4E IC50: 22.07 nM , induces apoptosis, and arrests the cell cycle at the G1 phase. PROTAC MNK1 degrader-1 has potent antitumor activity. PROTAC MNK1 degrader-1 has robust antileukemic efficacy in MV4-11 xenograft mice model with acceptable drug safety. Pink: MNK1 ligand HY-176429 ; Blue: CRBN ligase ligand HY-A0003 ; Black: linker HY-Y1139 ; CRBN + linker: HY-176430