NQ301

NQ301 is an antithrombotic agent; inhibits collagen-challenged rabbit platelet aggregation with an IC₅₀ of 10 mg/mL. IC50 & Target: IC50: 0.60±0.02 μM (collagen-challenged rabbit platelet aggregation), 0.58±0.04 μM (U46619-challenged rabbit platelet aggregation), 0.78±0.04 μM (arachidonic acid-challenged rabbit platelet aggregation)^[1] In Vitro: NQ301 concentration-dependently inhibits collagen (10 mg/mL)-, U46619 (1 mg/mL)- and arachidonic acid (100 mg/mL)-challenged rabbit platelet aggregation, with IC₅₀ values of 0.60±0.02, 0.58±0.04 and 0.78±0.04 μM, respectively. NQ301 potently suppresses thromboxane B₂ formation by platelets that are exposed to arachidonic acid in a concentration-dependent manner, but had no effect on the production of prostaglandin D₂, indicating an inhibitory effect on thromboxane A₂ synthase. NQ301 has a potential to inhibit thromboxane A₂ synthase activity with thromboxane A₂/prostaglandin H₂ receptor blockade, and modulate arachidonic acid liberation as well as 12-hydroxy-5,8,10,14-eicosatetraenoic acid formation in platelets^[1]. NQ301 inhibits platelet aggregation by suppression of the intracellular pathway, rather than by direct inhibition of fibrinogen-GPIIb/IIIa complex binding. NQ301 significantly inhibits the increase of cytosolic Ca²⁺ concentration and ATP secretion, and also significantly increases platelet cAMP levels in the activated platelets. The antiplatelet activity of NQ301 may be mediated by inhibition of cytosolic Ca²⁺ mobilization, enhancement of cAMP production and inhibition of ATP secretion in activated platelets^[2].