The effect of the new GSK-3B inhibitor on the processes of platelet adhesion, activation, secretion and aggregation

Thrombosis is a complex multi-stage process consisting of successive phases of adhesion, activation and aggregation of platelets. The platelet receptor landscape is represented by many subtypes of receptors and signaling pathways associated with their activation. One of the participants in these pathways is the GSK3P kinase, but its role and functions in the regulation of platelet activity remain a complex and not fully elucidated issue. The study of the antiplatelet activity of the GSK3G inhibitor of the K-167 compound showed no effect on platelet adhesion and P2Y1 activation. At the same time, K-167 inhibits aggregation mediated by GPVI and P2Y12 receptors with IC50 3.0 and 7.9 pM, respectively. The effect on thromboxane A2 and thrombin-induced aggregation is weak or absent, which confirms the GSK3li-mediated mechanism of action. It has been shown that an important aspect of the antiplatelet activity of this substance is the inhibition of the synthesis of thromboxane A2 in vivo and the suppression of the secretion of the contents of platelet granules.