Thromboxane A2

Thromboxane A2 is a type of thromboxane that is produced by activated platelets and has prothrombotic properties. It is a known vasoconstrictor and is especially important during tissue injury and inflammation. It is also regarded as responsible for Prinzmetal's angina.

ICI 185,282
106393-80-0
ICI 192,605
117621-64-4
L-670,596
121083-05-4
U 46619
56985-40-1
Ozagrel hydrochloride
74003-18-2
82571-53-7
Ozagrel
82571-53-7

Background


An Overview of Thromboxane A2

Thromboxane A2 is a prostaglandin derivative synthesized by thromboxane synthase after metabolism of arachidonic acid by cyclooxygenase, and is produced mainly by activated platelet stimulation in vivo. Thromboxane A2 is a major metabolite of arachidonic acid. Specifically, arachidonic acid is mainly found in cell membrane phospholipids. Under the action of lipoxygenase and cyclooxygenase, leukotriene and prostaglandin intermediate metabolite are produced. A variety of prostaglandin synthetases catalyze the production of thromboxane A2. Thromboboxane synthetase in platelets and macrophages catalyzes the conversion of intermediate metabolites of prostaglandins to thromboxane A2. Thromboxane A2 exerts biological effects in various tissues and cells by binding to seven transmembrane-coupled receptors (thromboxane A2 receptor, TP), and shows functions of promoting platelet aggregation, contraction of blood vessels, and mediating immune responses.

Thromboxane A2 and diseases

Thromboxane A2 induces platelet aggregation, contraction of blood vessels and airway smooth muscle, stimulates vascular smooth muscle mitosis and hypertrophy, and plays an important role in the pathogenesis of acute coronary syndrome, coronary heart disease, and pulmonary hypertension. The synthesis of thromboxane A2 is significantly increased in diabetic patients. Thromboxane A2 induces platelet aggregation by acting on thromboxane receptors, vasoconstriction, and thrombosis are involved in the development of cardiovascular complications in diabetes. In addition, thromboxane A2 is closely associated with diabetic nephropathy, acute kidney injury, chronic kidney disease, and renal transplant rejection.

Inhibition of Thromboxane A2

Thromboxane A2 modulators include epoxide synthase inhibitors, Thromboxane A2 synthetase inhibitors, TP antagonists, and some dual-target drugs. Aspirin is currently the most widely used non-selective epoxide synthase inhibitor. Thromboxane A2 synthetase inhibitors are mainly oxalic acid benzene (UK37248), picogrelag (CGS13080), ozagray (OKY046), CS-518 (RS5186), OKY1581, eppogree (CV4151), and furoic acid (U63557A). S18886 is an oral non-prostaglandin reversible TP antagonist that prevents atherosclerosis, reverses plaque, and improves endothelial function. BM-573 has dual activities of thromboxane A2 synthetase inhibitor and TP antagonist. It can effectively delay the formation of early atherosclerosis and reduce the area of atherosclerosis. The development of antithrombotic drugs based on the thromboxane A2 target will provide new targets for the treatment of diabetic cardiovascular complications and the development of new low-side antithrombotic drugs.

Reference:

Cheng, Y., Austin, S. C., Rocca, B., Koller, B. H., Coffman, T. M., Grosser, T., ... & FitzGerald, G. A. (2002). Role of prostacyclin in the cardiovascular response to thromboxane A2. Science, 296(5567), 539-541.