DU-14 is a highly potent and selective small molecule degrader for both PTP1B and TC-PTP with DC50 values of 4.3 and 4.8 nM, respectively, in HEK293 cells after 16 hours treatment.
DU-14 inhibits the phosphatase activity of PTP1B and TC-PTP with IC50 values of 24.2 nM and 30.1 nM, respectively.
DU-14 exhibits >88-fold selectivity for PTP1B and TC-PTP over a representative list of 12 PTPs, consisting of receptor-like, nonreceptor-like, and dual specific phosphatases.
DU-14 amplified IFN-γ induced pSTAT1/Y701 with EC50 of 76.2 nM, promoted CD8+ T cell activation.
DU-14 efficiently amplified IFN-γ signaling through inhibition of PTP1B and TC-PTP catalyzed yyrosine dephosphorylation of JAK2/Y1007/Y1008, JAK1/Y1034/Y1035 and/or STAT1/Y701, leading to increased cell surface MHC-I expression, which is required for efficient T-cell mediated killing of tumor cells.
DU-14 (25-50 mg/kg, i,p,) repressed MC38 tumor in mice, with nearly complete PTP1B and TC-PTP degradation in whole tumor homogenates.