HealthDay News – The pepducin PZ-128 offers rapid, specific, dose-dependent, and reversible inhibition of platelet protease-activated receptor-1, according to a study published online December 17 in Arteriosclerosis, Thrombosis, and Vascular Biology.

Paul A. Gurbel, MD, from the Sinai Hospital of Baltimore, and colleagues report on the first human use of a protease-activated receptor-1-based pepducin, which was administered to 31 patients with coronary artery disease or multiple coronary artery disease risk factors. The authors examined the safety, antiplatelet efficacy, and pharmacokinetics at baseline, during the first 24 hours, and at 7 to 10 days after dosing.

The researchers observed dose-dependent inhibitory effects of PZ-128 on platelet aggregation, stimulated by the protease-activated receptor-1 agonist SFLLRN at 30 minutes to 6 hours, with 20% to 40% inhibition at 0.3 mg/kg, 40% to 60% at 0.5 mg/kg, and ≥80% to 100% at 1 to 2 mg/kg. The inhibitory effects of 0.5 mg/kg PZ-128 were reversible; by 24 hours, recovery of aggregation to SFLLRN was 50%. PZ-128 had no significant effects on aggregation induced by AYPGKF, ADP, or collagen. PZ-128 had a plasma half-life of 1.3 to 1.8 hours and was not detectable in urine.

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“PZ-128 is a promising antiplatelet agent that provides rapid, specific, dose dependent, and reversible inhibition of platelet protease-activated receptor-1 through a novel intracellular mechanism,” the authors wrote.

Disclosures: Several authors disclosed financial ties to the pharmaceutical and medical device industries.


Gurbel PA, Bliden KP, Turner SE, et al. Cell-penetrating pepducin therapy targeting PAR1 in subjects with coronary artery disease. Arterioscler Thromb Vasc Biol. 2015. doi: ATVBAHA.115.306777.