PSI-697 is a potent, selective and orally bioavailable P-selectin antagonist with biacore IC50 of 150 uM. PSI-697 dose dependently inhibits the binding of human P-selectin to human P-selectin glycoprotein ligand-1, inhibiting 50% of binding at 50 to 125 microM. PSI-697 shows oral efficacy in mouse and rat models of atherogenesis and vascular injury. PSI-697 (50 mg/kg p.o.) significantly reduced the number of rolling leukocytes by 39% (P < 0.05) versus vehicle control in surgical inflammation rat model. PSI-697 (100 mg/kg p.o.) reduced thrombus weight by 18% (P < 0.05) relative to vehicle, without prolonging bleeding time, in rat venous thrombosis model.
