Compound 182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2, inhibits the catalytic activities of PTP1B and PTPN2 with IC50 of 0.63 and 0.58 nM, respectively.
Compound 182 is a classic competitive inhibitor of PTP1B and PTPN2, with Ki values of 0.34 and 0.26 nM respectively.
Compound 182 inhibits PTP1B and PTPN2 in a reversible manner.
Compound 182 exhibits >15,00-fold selectivity for PTP1B and PTPN2 over other PTP family members with the exception of PTPe, CDC14B and CDC14A for which it is >1,300-, >8,000- and >10,000-fold respectively more selective for PTP1B and PTPN2.
Compound 182 promotes TCR and cytokine signaling in T cells, significantly enhances T cell responses ex vivo.
Compound 182 (10 mg/kg every 2 days or 3 days, i.v.) effectively represses the growth of AT3-OVA syngeneic tumors in C57BL/6 mice without promoting overt immune-related toxicities.
Compound 182 increases both the infiltration and activation of T cells, as well as the recruitment of NK cells and B cells that promote anti-tumor immunity.