Therapeutic strategies for targeting PARs. PARs have been targeted with traditional orthosteric antagonists, such as vorapaxar for PAR1. In addition, PAR signaling may be inhibited at the initiation step by preventing the protease from cleaving the N terminus with blocking antibodies. Alternatively, pepducins target the intracellular face of the receptor to interfere with G-protein signaling. Parmodulins target the C-terminal eighth helix and have been selected to direct signaling to the cytoprotective pathways (β-arrestin) while blocking G_αq signaling.