OP-5244 is a potent and orally active inhibitor of CD73, with an IC50 of 0.25 nM. OP-5244 reverses immunosuppression through blocking of adenosine production, and has the potential for the cancer research.IC50 & Target:IC50: 0.25 nM (CD73)In Vitro: OP-5244 inhibits the production of adenosine (ADO), with an EC50 of 0.79±0.38 nM in H1568 (NSCLC) cells.
OP-5244 inhibits AMP hydrolysis to ADO in peripheral blood derived CD8+ T cells with an EC50 of 0.22 nM.
OP-5244 (4.1-1000 nM; 96 h) rescues AMP-suppressed CD8+ T cells proliferation and cytokine production.
OP-5244 (0.01 nM-10 μM) inhibits ADO production completely in human and murine cancer cell lines (H1568 and EMT6, respectively).In Vivo: OP-5244 (15 mg/kg/day; s.c. for 13 d) exhibits anti-tumor effects as a single agent as shown by the tumor growth inhibition in mice.
OP-5244 (150 mg/kg; p.o. twice daily for 16 d) increases CD8+ T cells infiltration and reverses immunosuppression in mice.
OP-5244 (0.2 mg/kg; i.v.) exhibits terminal elimination half-lives (rat 8.5, dog 0.82, cyno 4.6 h) due to moderate plasma clearance (rat 0.18, dog 1.22, cyno 0.05 L/kg/h) and low steady-state volume of distribution (rat 0.22, dog 0.29, cyno 0.10 L/kg/h).
OP-5244 (10 mg/kg; p.o.) exhibits Cmax (rat 0.82, dog 1.25, cyno 1.72 μM) and AUC (rat 1.96, dog 1.75, cyno 14.2 μM?h) .