PRT060318 inhibits arterial and venous thrombosis in the mouse. (A) PRT060318 (30 mg/kg oral) delays time to occlusion in carotid artery photochemical injury model (PRT060318, 58 ± 16 vs vehicle, 33 ± 12 minutes; P = .001). V.Ctl. indicates vehicle control. (B) PRT060318 (intravenous infusion) delays time to occlusion in FeCl3-injured mesenteric arteries (PRT060318, 13.4 ± 0.8 vs vehicle, 8.8 ± 1.1 minute; P = .011). (C) Inhibition of Syk by PRT060318 (30 mg/kg oral, n = 6) but not vehicle control (n = 5) prevents death after injection of a collagen + epinephrine mixture in WT mice. All vehicle control-treated animals died within 5 minutes of the intravenous. Injection, whereas 50% of the PRT060318-treated animals survived. (D) Tail bleeding times, performed by transecting the mouse tail 3 mm from the tip, are comparable in PRT060318 (30 mg/kg oral) and vehicle-treated mice (V. Ctl., n = 15; PRT060318, n = 14).
