Home
Resources
Publications
Antithrombotic Potential of Blockers of Store-Operated Calcium Channels in Platelets

Antithrombotic Potential of Blockers of Store-Operated Calcium Channels in Platelets

Roger van Kruchten, Attila Braun, Marion A H Feijge, Marijke J E Kuijpers, Ronmy Rivera-Galdos, Peter Kraft, Guido Stoll, Christoph Kleinschnitz, Edouard M Bevers, Bernhard Nieswandt, Johan W M Heemskerk

Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1717-23.

PMID: 22580895

Abstract:

Objective:
Platelet Orai1 channels mediate store-operated Ca(2+) entry (SOCE), which is required for procoagulant activity and arterial thrombus formation. Pharmacological blockage of these channels may provide a novel way of antithrombotic therapy. Therefore, the thromboprotective effect of SOCE blockers directed against platelet Orai1 is determined.
Methods and results:
Candidate inhibitors were screened for their effects on SOCE in washed human platelets. Tested antagonists included the known compounds, SKF96365, 2-aminoethyl diphenylborate, and MRS1845 and the novel compounds, Synta66 and GSK-7975A. The potency of SOCE inhibition was in the order of Synta66>2-aminoethyl diphenylborate>GSK-7975A>SKF96365>MRS1845. The specificity of the first 3 compounds was verified with platelets from Orai1-deficient mice. Inhibitory activity on procoagulant activity and high-shear thrombus formation was assessed in plasma and whole blood. In the presence of plasma, all 3 compounds suppressed platelet responses and restrained thrombus formation under flow. Using a murine stroke model, arterial thrombus formation was provoked in vivo by transient middle cerebral artery occlusion. Postoperative administration of 2-aminoethyl diphenylborate markedly diminished brain infarct size.
Conclusions:
Plasma-soluble SOCE blockers such as 2-aminoethyl diphenylborate suppress platelet-dependent coagulation and thrombus formation. The platelet Orai1 channel is a novel target for preventing thrombotic events causing brain infarction.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP835904513	Synta66		835904-51-3	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: