Journal article

Advantages of a selective beta-isofonn phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat

Sharelle A Sturgeon, Catherine Jones, James A Angus, Christine E Wright

EUROPEAN JOURNAL OF PHARMACOLOGY | ELSEVIER SCIENCE BV | Published : 2008

Abstract

Phosphoinositide 3-kinase (PI3K) beta has been shown to play a critical role in shear-induced arterial thrombosis. The anti-thrombotic effects of a beta isoform selective PI3K inhibitor, TGX221, were compared to the effects of non-selective PI3K inhibitors (LY294002 and wortmannin) and a PI3K delta inhibitor (IC87114) in the rat. TGX221 (2.5 mg/kg i.v.) abolished cyclic flow reductions in a Folts-like carotid artery stenosis preparation of thrombosis while not changing bleeding time, heart rate, blood pressure or carotid vascular conductance. In contrast, the PI3K non-selective isoform inhibitor, wortmannin (5 mg/kg i.v.) was as effective in abolishing cyclic flow reductions, but caused mark..

View full abstract