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 IC50 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 [1]. (Pink: PTP1B ligand; Blue: VHL ligand; Black: linker ).
In Vivo, DU-14 (PTP1B/TC-PTP PROTAC) (25-50 mg/kg; intraperitoneal injection; 10 days) has antitumor activity in a mouse model of colon cancer[1].
In Vitro, DU-14 (PTP1B/TC-PTP PROTAC) (0-1000 nM; 16 h) causes PTP1B/TC-PTP degradation and promotes STAT1 phosphorylation in IFN-γ-treated MC38 cells[1]. DU-14 (PTP1B/TC-PTP PROTAC) (48 h) effectively degrades TC-PTP and PTP1B in T cells and promotes the activation of T cells[1].
References:
[1]. Dong J, et al. Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy. Angew Chem Int Ed Engl. 2023 May 22;62(22):e202303818.
In Vivo, DU-14 (PTP1B/TC-PTP PROTAC) (25-50 mg/kg; intraperitoneal injection; 10 days) has antitumor activity in a mouse model of colon cancer[1].
In Vitro, DU-14 (PTP1B/TC-PTP PROTAC) (0-1000 nM; 16 h) causes PTP1B/TC-PTP degradation and promotes STAT1 phosphorylation in IFN-γ-treated MC38 cells[1]. DU-14 (PTP1B/TC-PTP PROTAC) (48 h) effectively degrades TC-PTP and PTP1B in T cells and promotes the activation of T cells[1].
References:
[1]. Dong J, et al. Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy. Angew Chem Int Ed Engl. 2023 May 22;62(22):e202303818.