XXXX receptors--targets for developing antithrombotic agents.

@entity3076 @entity54154 @entity23998 @entity33507 @entity19 @entity1396 @entity1397 @entity37502 @entity11940 @entity460 @entity857 @entity3211
Platelet P2 receptors-- @entity23998 , @entity33507 , and P2X1--constitute the means by which @entity3211 can activate platelets. Coactivation of the Galphaq-coupled @entity23998 and @entity11940 -coupled @entity33507 receptors is necessary for @entity857 -mediated platelet activation, which forms the basis of using P2 antagonists as antithrombotic drugs. @entity23998 antagonists inhibit platelet activation, while @entity23998 knockout @entity19 show longer bleeding times than normal @entity19 but few other problems; however, its ubiquitous expression in other tissues renders @entity23998 questionable as an antithrombotic target. The @entity33507 receptor is expressed nearly exclusively in platelets and brain, making it an attractive antithrombotic target. Antagonists for the @entity33507 receptor have been developed that either require metabolic activation to covalently inhibit @entity33507 and are irreversible, or simply are competitive in nature and thus reversible. @entity1396 and @entity1397 are irreversible @entity33507 antagonists and have been repeatedly proven as clinical antithrombotic agents. In addition, a recently reported @entity33507 antagonist, @entity3076 , shows promise as a future antithrombotic drug. The AR-C series of compounds represent reversible @entity33507 antagonists and have been used extensively to characterize the function of @entity33507 in platelets. Clinical studies show that AR-C69931MX is as effective as @entity1397 ; furthermore, the combination of @entity37502 (cangrelor) and @entity1397 confers greater antagonism of @entity33507 than either antagonist alone. The @entity54154 is a @entity460 channel that functions to potentiate agonist-induced platelet shape change, and its inhibition or loss has little if any effect on hemostasis. A combination of @entity23998 and @entity33507 antagonists may represent an additional course of antithrombotic treatment.
