Overview of PAR1 modulators. (A) Thrombin activation of PAR1 triggers coupling to Gαq, Gα12/13, and β-arrestin 2 leading to cytodisruptive effects. (B) aPC activation of PAR1 selectively triggers coupling to Gα12/13 and β-arrestin 2 but not Gαq and elicits cytoprotective effects. (C) Orthosteric inhibitors (eg, vorapaxar, atopaxar) block the ligand binding pocket and completely block intracellular signaling. (D) Parmodulins target the intracellular surface of PAR1 and selectively inhibit some (eg, Gαq) but not all downstream signaling pathways, mimicking the effect of aPC.
Figure 2.

Overview of PAR1 modulators. (A) Thrombin activation of PAR1 triggers coupling to Gαq, Gα12/13, and β-arrestin 2 leading to cytodisruptive effects. (B) aPC activation of PAR1 selectively triggers coupling to Gα12/13 and β-arrestin 2 but not Gαq and elicits cytoprotective effects. (C) Orthosteric inhibitors (eg, vorapaxar, atopaxar) block the ligand binding pocket and completely block intracellular signaling. (D) Parmodulins target the intracellular surface of PAR1 and selectively inhibit some (eg, Gαq) but not all downstream signaling pathways, mimicking the effect of aPC.

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