{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:00:31Z","timestamp":1761541231508},"reference-count":23,"publisher":"Georg Thieme Verlag KG","issue":"02","funder":[{"name":"INSERM, EFS, ARMESA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>EP217609 is a new synthetic parenteral dual-action anticoagulant combining a direct thrombin inhibitor (\u03b1-NAPAP analog), an indirect factor Xa inhibitor (fondaparinux analog) and a biotin moiety allowing its neutralisation. EP217609 exhibited similar in vitro anticoagulant properties as its parent compounds. On the basis of dose-response curves, we identified low and moderate doses of EP217609 resulting in similar ex vivo prolongation of the APTT as \u03b1-NAPAP analog and comparable ex vivo anti-FXa activity as fondaparinux. The effects of EP217609 were compared to those of its parent compounds used alone or in combination in two models of experimental thrombosis induced by FeCl3 injury of the carotid artery or mechanical injury of atherosclerotic plaques in ApoE-deficient mice. When administered at low doses increasing the APTT by only 1.1 fold, EP217609 significantly reduced the thrombus area in both models as compared to \u03b1-NAPAP analog or fondaparinux alone, but not to the combination of these drugs. In contrast, at higher doses increasing the APTT 1.5 times, EP217609 was not superior to either parent compound. Low doses of EP217609 did not prolong the tail bleeding time or increase the volume of blood loss, although a tendency towards an increased blood loss was observed in five out of 12 mice. Finally, the effects of EP217609 could be neutralised in vivo by injection of avidin. The pharmacological profile of EP217609, its performance in arterial thrombosis models and its possible neutralisation make it an interesting molecule and a potential candidate as an antithrombotic drug.<\/jats:p>","DOI":"10.1160\/th14-05-0399","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T03:36:27Z","timestamp":1415244987000},"page":"385-395","source":"Crossref","is-referenced-by-count":7,"title":["EP217609, a neutralisable dual-action FIIa\/FXa anticoagulant, with antithrombotic effects in arterial thrombosis"],"prefix":"10.1160","volume":"113","author":[{"given":"Ghina","family":"Alame","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre H.","family":"Mangin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Freund","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Riehl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Magnenat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurice","family":"Petitou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9atrice","family":"Hechler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Gachet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,11,27]]},"reference":[{"key":"10.1160\/TH14-05-0399-1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0656"},{"key":"10.1160\/TH14-05-0399-2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0658"},{"key":"10.1160\/TH14-05-0399-3","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0689"},{"key":"10.1160\/TH14-05-0399-4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.3.1522"},{"key":"10.1160\/TH14-05-0399-5","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200300640"},{"key":"10.1160\/TH14-05-0399-6","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPQOD9WFPEYY0H"},{"key":"10.1160\/TH14-05-0399-7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00351.x"},{"key":"10.1160\/TH14-05-0399-8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1160\/TH09-01-0063","volume":"102","author":"Petitou","year":"2009","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH14-05-0399-9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-381764"},{"key":"10.1160\/TH14-05-0399-10","unstructured":"Neuhart E, Gueret P, Krezel C, et al. Neutralizable parenteral anticoagulation: EP217609 and its specific antidote, avidin, in healthy subjects. A new paradigm ? XXIIIrd Congress of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2011; 9 (Suppl 2): 106 (Abstract)"},{"key":"10.1160\/TH14-05-0399-11","unstructured":"Fromes I, Neuhart E, Krezel C, et al. EP217609, a new neutralizable anticoagulant for cardiopulmonary bypass during cardiac surgery. 65th congress of the French Society for Thoracic and Cardiovascular Surgery 2010: C-10 (Abstract)"},{"key":"10.1160\/TH14-05-0399-12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04218.x"},{"key":"10.1160\/TH14-05-0399-13","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(90)90106-M"},{"key":"10.1160\/TH14-05-0399-14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080184"},{"key":"10.1160\/TH14-05-0399-15","doi-asserted-by":"publisher","DOI":"10.1160\/THS10-11-0730"},{"key":"10.1160\/TH14-05-0399-16","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.98.4_301"},{"key":"10.1160\/TH14-05-0399-17","doi-asserted-by":"publisher","DOI":"10.3109\/14756369509040681"},{"key":"10.1160\/TH14-05-0399-18","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12453"},{"key":"10.1160\/TH14-05-0399-19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03089.x"},{"key":"10.1160\/TH14-05-0399-20","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2010.0797"},{"key":"10.1160\/TH14-05-0399-21","unstructured":"Gueret P, Krezel C, van Giersbergen PLM, et al. First human study with EP217609, a new synthetic parenteral neutralizable dual action anticoagulant. Pathophysiol Haemost Thromb 2009\/2010; 37: P177 (Abstract)"},{"key":"10.1160\/TH14-05-0399-22","unstructured":"Shore-Lesserson L, Gravlee G. Anticoagulation for cardiopulmonary bypass. In: Cardiopulmonary Bypass: Principles and Practice, 2nd ed. Lippincott, Williams & Wilkins 2008; pp. 472-501"},{"key":"10.1160\/TH14-05-0399-23","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.142810"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH14-05-0399.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T22:54:54Z","timestamp":1565996094000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH14-05-0399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":23,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2017,11,21]]},"published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1160\/th14-05-0399","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3]]}}}