The Novel Oral Syk Inhibitor, Bl1002494, Protects Mice From Arterial Thrombosis and Thromboinflammatory Brain Infarction

• DOI: 10.1161/atvbaha.115.306883
• Publication Date: 2016-04-22T03:54:18Z
• Authors: Judith M.M. van E...; David Stegner; David J. Lamb; Peter Kraft; Sarah Beck; Ina Thielmann; Friedemann Kiefer; Barbara Walzog; Guido Stoll; Bernhard Nieswandt
• Keywords: GPVI; Stroke

Ischemic stroke, which is mainly caused by thromboembolic occlusion of brain arteries, the second leading cause death and disability worldwide with limited treatment options. The platelet collagen receptor glycoprotein VI (GPVI) a key player in arterial thrombosis critical determinant stroke outcome, making its signaling pathway an attractive target for pharmacological intervention. spleen tyrosine kinase (Syk) essential mediator downstream not only GPVI but also other immune cell receptors. We sought to assess whether Syk might be effective antithrombotic target.We demonstrate that mice lacking platelets specifically are protected from thrombus formation ischemic display unaltered hemostasis. Furthermore, we show treated novel, selective, orally bioavailable inhibitor BI1002494 were model had smaller infarct sizes significantly better neurological outcome 24 hours after transient middle cerebral artery occlusion, when was administered therapeutically, is, ischemia.These results provide direct evidence inhibition safe therapeutic strategy prevent limit progression acute stroke.