TXA2R Activators

TXA2R activators are a group of chemicals that either directly bind to and activate the thromboxane A2 receptor (TXA2R) or can indirectly lead to its activation via their interactions with related signaling pathways. These chemicals can be divided into several categories based on their structures and mechanisms of action. The first category includes arachidonic acid and its metabolites, such as thromboxane A2 and isoprostanes. These are endogenous substances that can directly bind to and activate TXA2R. Arachidonic acid is converted into thromboxane A2 via the cyclooxygenase (COX) pathway, and thromboxane A2 can then bind to and activate TXA2R. Isoprostanes, on the other hand, are formed by the non-enzymatic oxidation of arachidonic acid, and certain isoprostanes can also bind to and activate TXA2R. The second category includes synthetic analogs of thromboxane A2 and prostacyclin, such as U46619, carbaprostacyclin, and iloprost. U46619 is a stable analog of thromboxane A2 and can directly activate TXA2R. Carbaprostacyclin and iloprost are analogs of prostacyclin, which isanother arachidonic acid metabolite. They primarily activate the prostacyclin receptor (IP), but can also interact with TXA2R, especially under certain conditions. The third category includes chemicals that are primarily antagonists of TXA2R but can paradoxically activate the receptor under certain conditions. This group includes sulotroban, seratrodast, ifetroban, terbogrel, ramatroban, S-145, and GR 32191. These chemicals are designed to block TXA2R, but they can activate the receptor through a mechanism known as "functional selectivity" or "biased agonism". This process implies that these antagonists can induce a conformational change in TXA2R, leading to a response that is different from that produced by the natural ligand.