Structural highlights
Publication Abstract from PubMedTicagrelor is a direct acting reversibly binding P2Y12 antagonist and is widely used as an antiplatelet therapy for the prevention of cardiovascular events in acute coronary syndrome patients. However, antiplatelet therapy can be associated with an increased risk of bleeding. Here we present data on the identification, in vitro and in vivo pharmacology of a Fab antidote for ticagrelor. The Fab has a 20 pM affinity for ticagrelor, which is 100 times stronger than ticagrelor's affinity for its target P2Y12. Despite ticagrelor's structural similarities to adenosine, the Fab is highly specific and does not bind to adenosine, ATP, ADP or structurally related drugs. The antidote concentration-dependently neutralized the free fraction of ticagrelor and reversed its antiplatelet activity both in vitro in human platelet rich plasma and in vivo in mice. Finally, the antidote proved effective in normalizing ticagrelor dependent bleeding in a mouse model of acute surgery. This specific antidote for ticagrelor may prove a valuable agent for patients who require emergency procedures. Structural and functional characterisation of a specific antidote for ticagrelor.,Buchanan A, Newton P, Pehrsson S, Inghardt T, Antonsson T, Svensson P, Sjogren T, Oster L, Janefeldt A, Sandinge AS, Keyes F, Austin M, Spooner J, Gennemark P, Penney M, Howells G, Vaughan T, Nylander S Blood. 2015 Mar 18. pii: blood-2015-01-622928. PMID:25788700[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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