YM-254890, a Natural Gq/11 Protein Inhibitor, Inhibits Platelet Aggregation

Platelets play a crucial role in thrombus formation, particularly in the arterial system. Antiaggregant is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. Moreover, antiplatelet is an essential therapy in post-coronary stenting patients.When the vascular endothelium ruptures, platelets adhere to subendothelial components, and this induces platelet aggregation. The adherent platelets spread over the surface and release their dense granule contents including ADP, thromboxane A2, and serotonin. These agonists then activate surrounding platelets, leading to thrombus formation. Especially, YM-254890 is a specific G(alpha)q/11 inhibitor. In particular, YM-254890 is useful for treating peripheral arterial disease. As a result, YM-254890 significantly reduces systemic blood pressure.

Antiplatelet agents inhibit platelet activation and may be useful in the treatment of these diseases. Of these, YM-254890 is a platelet aggregation inhibitor produced by Chromobacterium sp. QS3666. YM-254890 inhibits platelet aggregation induced by ADP (2, 5 and 20 μM) in human platelet-rich plasma with IC50 values of 0.37, 0.39 and 0.51 μM, respectively.

Furthermore, researchers examined the antithrombotic and thrombolytic effects of the G(q/11) inhibitor YM-254890 in an electrically-induced carotid artery thrombosis model in rats. YM-254890 dose-dependently inhibits ex vivo ADP-induced platelet aggregation after intravenous injection bolus injection. YM-254890 (10 μg/kg) significantly improves carotid patency status after thrombolysis. However, YM-254890 (30 μg/kg) decreases systemic blood pressure. In the thrombolysis study, YM-254890 (30 μg/kg; intravenous injection) shortens the time to reperfusion and prevents re-occlusion after thrombolysis with a modified tissue-type plasminogen activator.

To summarise, YM-254890 is effective for treating G(q)-mediated diseases, and YM-254890 is a useful tool for investigating the biological roles of G(q/11).

Taniguchi M, et al. YM-254890, a novel platelet aggregation inhibitor produced by Chromobacterium sp. QS3666. J Antibiot (Tokyo). 2003 Apr;56(4):358-63.