DU-14 (PTP1B/TC-PTP PROTAC ) is a potent and selective PTP1B and TC-PTP dual PROTAC degrader. DU-14 (PTP1B/TC-PTP PROTAC ) has the IC 50 for PTP1B and TC-PTP phosphatase activity of 24.2 nM and 30.1 nM, respectively. DU-14 (PTP1B/TC-PTP PROTAC ) enhances IFN-γ signaling, promotes T cell activation, and has anti-tumor activity. (Pink: PTP1B/TC-PTP inhibitor ; Black: Linker ; Blue: E3 ligand ).