5alc

Ticagrelor antidote candidate Fab 72 in complex with ticagrelor

spinqualitylabelsall models 5alc, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5alc is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: TIQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Ticagrelor 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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