{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:11:57Z","timestamp":1790838717072,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,9]],"date-time":"2015-11-09T00:00:00Z","timestamp":1447027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb\/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound.<\/jats:p>","DOI":"10.3390\/md13116774","type":"journal-article","created":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T02:38:30Z","timestamp":1447209510000},"page":"6774-6791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity"],"prefix":"10.3390","volume":"13","author":[{"given":"Emmanuel","family":"Ampofo","sequence":"first","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sp\u00e4ter","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Hemostasiology and Transfusion Medicine, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Eichler","sequence":"additional","affiliation":[{"name":"Institute for Hemostasiology and Transfusion Medicine, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Menger","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Laschke","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1006\/bbrc.2000.3349","article-title":"Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product","volume":"275","author":"Soni","year":"2000","journal-title":"Biochem. 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