PPACK

PPACK is a potent, peptidic inhibitor targeting thrombin and granzyme GZMK. PPACK specifically blocks the activities of thrombin and GZMK, thereby inhibiting thrombin-mediated PAR-1 cleavage, as well as downstream inflammatory and procoagulant signaling pathways. Through stabilizing IκB proteins, blocking NF-κB activation and reducing systemic levels of proinflammatory/procoagulant biomarkers, PPACK exerts multiple effects including anti-inflammatory, antithrombotic, barrier repair, and inhibition of atherosclerotic plaque progression. PPACK binds to platelets without interference from kininogen, effectively limiting acute thrombus growth and reducing eosinophil infiltration and goblet cell hyperplasia in asthma models. PPACK is an important tool molecule for investigating the mechanisms of atherosclerosis, asthma and related thromboinflammatory diseases^[1][2][3][4].
In Vitro:PPACK nanoparticles completely inhibit thrombin-induced cleavage of the PAR-1 receptor on human aortic endothelial cells, as well as tissue factor expression on the surface of THP-1 monocytes^[1].
PPACK nanoparticles inhibit thrombin-induced NF-κB activation in human aortic endothelial cells and THP-1 monocytes^[1].
PPACK (5-fold molar excess; room temperature; 1 h) inactivates the amidolytic activity of human α-thrombin after 1 h of incubation at room temperature, generating PPACK-thrombin that does not interfere with the enzymatic function of unmodified α-thrombin^[4].
PPACK (200 μM, 100 μM, 10 μM) exerts anticoagulant effects, and exhibits stronger anticoagulant activity on a molar basis than the factor Xa inhibitor GGACK (HY-137495) used alone at the same concentrations^[5]. In Vivo:Intravenous administration of PPACK nanoparticles (intravenous injection; 3 times per week; for 4 consecutive weeks) to high-fat diet-fed ApoE knockout mice reduces vascular procoagulant activity, restores endothelial barrier integrity, delays plaque progression, and attenuates inflammatory signaling in atherosclerotic plaques, without inducing systemic anticoagulation or altering serum cholesterol levels^[1].
PPACK (62.5 μg; i.p.; every 2 days; 8 to 18 days post-immunization) significantly attenuates airway eosinophilia, goblet cell hyperplasia and airway hyperresponsiveness in a mouse model of asthma^[3].