Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times

扎鲁司特是一种广谱硫醇异构酶抑制剂,可抑制血栓形成而不改变出血时间

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作者:Lisa-Marie Holbrook, Shirley J Keeton, Parvathy Sasikumar, Sophie Nock, Justine Gelzinis, Elizabeth Brunt, Sarah Ryan, Megan M Pantos, Christina A Verbetsky, Jonathan M Gibbins, Daniel R Kennedy

Background and purpose

Multiple members of the thiol isomerase (TI) family of enzymes are present in and released by platelets. Inhibition of these enzymes

Purpose

Multiple members of the thiol isomerase (TI) family of enzymes are present in and released by platelets. Inhibition of these enzymes

Results

When applied to platelets, zafirlukast diminished platelet responses in vitro. Zafirlukast was antithrombotic in murine models of thrombosis but did not impair responses in a model of haemostasis. Since TIs are known to modulate adhesion receptor function, we explored the effects of zafirlukast on cell migration. This was inhibited independently of cysteinyl LT receptor expression and was associated with modulation of cell-surface free thiol levels consistent with alterations in redox activity on the cell surface.

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