Inhibition of platelet aggregation (IPA) in the 0.5 mg/kg PZ-128 dose cohort to 8, 12, and 20 μmol/L protease-activated receptor-1 (PAR1) agonist peptide, SFLLRN. A, The structure of the PZ-128 pepducin9 (green) aligns closely (backbone root mean square deviation 1.4 Å) with the i3-loop/cytoplasmic α-helical extension of TM6 based on the rhodopsin25,26 (red), and PAR1-vorapaxar27 (blue) x-ray structures. Ex vivo aggregation was conducted in platelet-rich plasma by standard light transmission aggregometry and maximal and final (at 6–7 minutes) aggregation (mean±SD) normalized to baseline (t=0) for each agonist for (B) all subjects, and the subset receiving (C) aspirin (acetylsalicylic acid [ASA]).