Direct inhibitors of GPIIb-IIIa binding include antithrombotics such as eptifibatide (Integrelin), abciximab (Reopro), and tirofiban (Aggrestat), drugs that reduce thrombosis, or formation of blood clots, by binding to the receptors and completely blocking their function. However, long-term administration of similar drugs doesn't work, in part because of the risk of serious bleeding complications in chronic use.
In sharp contrast, drugs such as clopidogrel (Plavix) and aspirin are two examples of antithrombotics that work well in chronic administration and are widely used for this purpose.
"Drugs such as aspirin and clopidogrel work in large part by blocking the activation of GPIIb-IIIa. These drugs don't work directly on GPIIb-IIIa, but do block signaling pathways that indirectly contribute to GPIIb-IIIa activation. Thus, they achieve a chronic anti-thrombotic effect with acceptable risk of bleeding ," said Ginsberg. He and his colleagues asked themselves if there was another way to block the receptors, by working at the step of activation when the receptors change from non-sticky to sticky ?in other words, by blocking the ability of GPIIb-IIIa to activate.
"Up until now, scientists have had a limited understanding of the pathways leading to platelet integrin activation, though we have developed a long list of what might impact the activation process," said Ginsberg. When cultured cells were engineered to express GPIIb-IIIa, agents that usually activated the platelet integrin failed to do so. The UCSD researchers realized that there was something missing, something special about platelets that impacted the activation process.
In 2003, Ginsberg, and Sanford Shattil, M.D., UCSD professor of medicine and Chief of Hematology/Oncology, and colleagues published a paper in the journal Science about the discovery that talin ? a large cytoplasmic protein that binds to the inside of an integrin or family of integrins ?delive
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Source:University of California - San Diego