tcY-NH2 is a synthetic peptide antagonist of proteinase-activated receptor 4 (PAR4) that corresponds to amino acids 1-6 of the amino terminal tethered ligand sequence of mouse PAR4.1 It inhibits platelet aggregation induced by the PAR4 agonist AYPGKF-NH2 in washed isolated rat platelets (IC50 = 95-190 µM), as well as induces relaxation of isolated rat aortic rings precontracted with phenylephrine and contraction of isolated rat gastric longitudinal muscle strips (EC50s = 64 and 1 µM, respectively). tcY-NH2 (400 µM) inhibits thrombin-induced migration of primary hepatocellular carcinoma (HCC) cells.2 It reduces myocardial infarct size as a percentage of the area at risk ex vivo in a isolated rat heart model of ischemia-reperfusion injury.3
1.Hollenberg, M.D., Saifeddine, M., Sandhu, S., et al.Proteinase-activated receptor-4: Evaluation of tethered ligand-derived peptides as probes for receptor function and as inflammatory agonists in vivoBr. J. Pharmacol.143(4)443-454(2004) 2.Kaufmann, R., Rahn, S., Pollrich, K., et al.Thrombin-mediated hepatocellular carcinoma cell migration: Cooperative action via proteinase-activated receptors 1 and 4J. Cell. Physiol.211(3)699-707(2007) 3.Strande, J.L., Hsu, A., Su, J., et al.Inhibiting protease-activated receptor 4 limits myocardial ischemia/reperfusion injury in rat hearts by unmasking adenosine signalingJ. Pharmacol. Exp. Ther.324(3)1045-1054(2008)