{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:01:54Z","timestamp":1761541314685,"version":"3.37.3"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":259,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"Brazilian National Council for Scientific and Technological Development"},{"name":"State of Rio de Janeiro Research Foundation","award":["E26\/010.003016\/2014","CNE E26\/201.426\/2014"],"award-info":[{"award-number":["E26\/010.003016\/2014","CNE E26\/201.426\/2014"]}]},{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel","doi-asserted-by":"crossref","award":["63\/2010"],"award-info":[{"award-number":["63\/2010"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon"],"published-print":{"date-parts":[[2016,9]]},"DOI":"10.1016\/j.toxicon.2016.05.007","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T17:47:07Z","timestamp":1462988827000},"page":"46-51","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Exploiting the antithrombotic effect of the (pro)thrombin inhibitor bothrojaracin"],"prefix":"10.1016","volume":"119","author":[{"given":"Mariane","family":"Assafim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via S.","family":"Frattani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos S.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dione M.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robson Q.","family":"Monteiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-6923","authenticated-orcid":false,"given":"Russolina B.","family":"Zingali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxicon.2016.05.007_bib1","doi-asserted-by":"crossref","first-page":"9083","DOI":"10.1021\/bi960043l","article-title":"Bothrojaracin: a potent two-site-directed thrombin inhibitor","volume":"35","author":"Arocas","year":"1996","journal-title":"Biochemistry"},{"key":"10.1016\/j.toxicon.2016.05.007_bib2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1432-1033.1997.00550.x","article-title":"Molecular cloning and expression of bothrojaracin, a potent thrombin inhibitor from snake venom","volume":"248","author":"Arocas","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.toxicon.2016.05.007_bib3","doi-asserted-by":"crossref","first-page":"e0004298","DOI":"10.1371\/journal.pntd.0004298","article-title":"In\u00a0vitro mode of action and anti-thrombotic activity of boophilin, a multifunctional kunitz protease inhibitor from the midgut of a tick vector of babesiosis, Rhipicephalus microplus","volume":"10","author":"Assump\u00e7\u00e3o","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"issue":"Suppl.\u00a01","key":"10.1016\/j.toxicon.2016.05.007_bib4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1538-7836.2007.02496.x","article-title":"Exosites in the substrate specificity of blood coagulation reactions","volume":"5","author":"Bock","year":"2007","journal-title":"J.\u00a0Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1742-4658.2009.07494.x","article-title":"Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in\u00a0vivo","volume":"277","author":"Calvo","year":"2010","journal-title":"FEBS J."},{"key":"10.1016\/j.toxicon.2016.05.007_bib6","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S0041-0101(99)00087-2","article-title":"Identification of bothrojaracin-like proteins in snake venoms from Bothrops species and Lachesis muta","volume":"37","author":"Castro","year":"1999","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib7","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/jth.12797","article-title":"Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity","volume":"13","author":"Chen","year":"2015","journal-title":"J.\u00a0Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib8","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1161\/ATVBAHA.112.253906","article-title":"Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in\u00a0vivo","volume":"32","author":"Collin","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.toxicon.2016.05.007_bib9","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCRESAHA.112.264903","article-title":"Translational success stories: development of direct thrombin inhibitors","volume":"111","author":"Coppens","year":"2012","journal-title":"Circ. Res."},{"key":"10.1016\/j.toxicon.2016.05.007_bib10","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.toxicon.2009.12.003","article-title":"Platelet aggregation inhibitors from hematophagous animals","volume":"56","author":"Francischetti","year":"2010","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/10739680701451516","article-title":"Blood coagulation, inflammation, and malaria","volume":"15","author":"Francischetti","year":"2008","journal-title":"Microcirculation"},{"key":"10.1016\/j.toxicon.2016.05.007_bib12","doi-asserted-by":"crossref","first-page":"16678","DOI":"10.1021\/bi991231p","article-title":"Anophelin: kinetics and mechanism of thrombin inhibition","volume":"38","author":"Francischetti","year":"1999","journal-title":"Biochemistry"},{"key":"10.1016\/j.toxicon.2016.05.007_bib13","doi-asserted-by":"crossref","first-page":"16216","DOI":"10.1016\/S0021-9258(19)85408-X","article-title":"A\u00a0Kazal-type inhibitor with thrombin specificity from Rhodnius prolixus","volume":"268","author":"Friedrich","year":"1993","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.toxicon.2016.05.007_bib14","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1161\/01.RES.79.3.590","article-title":"Biochemical and pharmacological properties of SANORG 32701. Comparison with the \u201csynthetic pentasaccharide\u2019 (SR 90107\/ORG 31540) and standard heparin","volume":"79","author":"Herbert","year":"1996","journal-title":"Circ. Res."},{"key":"10.1016\/j.toxicon.2016.05.007_bib15","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1160\/TH13-10-0811","article-title":"Natural inhibitors of thrombin","volume":"111","author":"Huntington","year":"2014","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib16","doi-asserted-by":"crossref","first-page":"e0133991","DOI":"10.1371\/journal.pone.0133991","article-title":"Identification and mechanistic analysis of a novel tick-derived inhibitor of thrombin","volume":"10","author":"Jablonka","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.toxicon.2016.05.007_bib17","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.thromres.2015.06.001","article-title":"Risk of stent thrombosis and major bleeding with bivalirudin compared with active control: a systematic review and meta-analysis of randomized trials","volume":"136","author":"Kianoush","year":"2015","journal-title":"Thromb. Res."},{"issue":"Suppl.\u00a01","key":"10.1016\/j.toxicon.2016.05.007_bib18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1538-7836.2011.04279.x","article-title":"Toxins in thrombosis and haemostasis: potential beyond imagination","volume":"9","author":"Kini","year":"2011","journal-title":"J.\u00a0Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib19","doi-asserted-by":"crossref","first-page":"29101","DOI":"10.1074\/jbc.M705600200","article-title":"Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick","volume":"282","author":"Koh","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.toxicon.2016.05.007_bib20","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.toxicon.2011.03.017","article-title":"From snake venom toxins to therapeutics \u2013 cardiovascular examples","volume":"59","author":"Koh","year":"2012","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib21","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.3892\/mmr.2014.2025","article-title":"Direct thrombin inhibitors: patents 2002\u20132012","volume":"9","author":"Kong","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.toxicon.2016.05.007_bib22","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.toxicon.2005.02.013","article-title":"Jararhagin and its multiple effects on hemostasis","volume":"45","author":"Laing","year":"2005","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib23","doi-asserted-by":"crossref","first-page":"e00064","DOI":"10.1042\/BSR20130057","article-title":"Activation of blood coagulation in cancer: implications for tumour progression","volume":"33","author":"Lima","year":"2013","journal-title":"Biosci. Rep."},{"key":"10.1016\/j.toxicon.2016.05.007_bib24","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1182\/blood-2013-08-517474","article-title":"Desmolaris, a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in\u00a0vivo","volume":"122","author":"Ma","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.toxicon.2016.05.007_bib25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.thromres.2003.10.014","article-title":"Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor","volume":"112","author":"Mendes-Silva","year":"2003","journal-title":"Thromb. Res."},{"key":"10.1016\/j.toxicon.2016.05.007_bib26","doi-asserted-by":"crossref","first-page":"e0003869","DOI":"10.1371\/journal.pntd.0003869","article-title":"Salivary thromboxane A2-binding proteins from triatomine vectors of chagas disease inhibit platelet-mediated Neutrophil Extracellular Traps (NETs) formation and arterial thrombosis","volume":"9","author":"Mizurini","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.toxicon.2016.05.007_bib27","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1160\/TH10-03-0186","article-title":"Nitrophorin 2, a factor IX(a)-directed anticoagulant, inhibits arterial thrombosis without impairing haemostasis","volume":"104","author":"Mizurini","year":"2010","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib28","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1110\/ps.09001","article-title":"Characterization of bothrojaracin interaction with human prothrombin","volume":"10","author":"Monteiro","year":"2001","journal-title":"Protein Sci."},{"key":"10.1016\/j.toxicon.2016.05.007_bib29","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0041-0101(96)00176-6","article-title":"Distinct bothrojaracin isoforms produced by individual jararaca (Bothrops jararaca) snakes","volume":"35","author":"Monteiro","year":"1997","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib30","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1006\/bbrc.1999.1297","article-title":"Allosteric changes of thrombin catalytic site induced by interaction of bothrojaracin with anion-binding exosites I and II. Biochem","volume":"262","author":"Monteiro","year":"1999","journal-title":"Biophys. Res. Commun."},{"key":"10.1016\/j.toxicon.2016.05.007_bib31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/abbi.2000.2006","article-title":"Inhibition of prothrombin activation by bothrojaracin, a C-type lectin from Bothrops jararaca venom","volume":"382","author":"Monteiro","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.toxicon.2016.05.007_bib32","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1055\/s-0037-1612987","article-title":"Bothrojaracin, a proexosite I ligand, inhibits factor Va-accelerated prothrombin activation","volume":"87","author":"Monteiro","year":"2002","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1160\/TH06-02-0105","article-title":"Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade","volume":"96","author":"Nazareth","year":"2006","journal-title":"Thromb. Haemost."},{"issue":"Pt 3","key":"10.1016\/j.toxicon.2016.05.007_bib34","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1042\/bj2800805","article-title":"A\u00a0novel one-step purification of human alpha-thrombin after direct activation of crude prothrombin enriched from plasma","volume":"280","author":"Ngai","year":"1991","journal-title":"Biochem. J."},{"key":"10.1016\/j.toxicon.2016.05.007_bib35","doi-asserted-by":"crossref","first-page":"28629","DOI":"10.1074\/jbc.270.48.28629","article-title":"Triabin, a highly potent exosite inhibitor of thrombin","volume":"270","author":"Noeske-Jungblut","year":"1995","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.toxicon.2016.05.007_bib36","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1161\/CIRCULATIONAHA.112.128413","article-title":"Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement","volume":"127","author":"Pagidipati","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.toxicon.2016.05.007_bib37","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1021\/bi900921t","article-title":"Mutagenesis studies toward understanding allostery in thrombin","volume":"48","author":"Qureshi","year":"2009","journal-title":"Biochemistry"},{"key":"10.1016\/j.toxicon.2016.05.007_bib38","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.toxicon.2008.03.018","article-title":"Haematological evaluation of patients bitten by the jararaca, Bothrops jararaca, in Brazil","volume":"51","author":"Santoro","year":"2008","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib39","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0049-3848(89)90210-7","article-title":"Comparison of two experimental thrombosis models in rats effects of four glycosaminoglycans","volume":"54","author":"Vogel","year":"1989","journal-title":"Thromb. Res."},{"key":"10.1016\/j.toxicon.2016.05.007_bib40","doi-asserted-by":"crossref","first-page":"e1004338","DOI":"10.1371\/journal.ppat.1004338","article-title":"Plasmodium falciparum infection induces expression of a mosquito salivary protein (Agaphelin) that targets neutrophil function and inhibits thrombosis without impairing hemostasis","volume":"10","author":"Waisberg","year":"2014","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.toxicon.2016.05.007_bib41","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1160\/TH07-10-0644","volume":"99","author":"Warkentin","year":"2008","journal-title":"Bivalirudin. Thromb. Haemost."},{"key":"10.1016\/j.toxicon.2016.05.007_bib42","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.toxicon.2005.02.030","article-title":"Snake venoms and coagulopathy","volume":"45","author":"White","year":"2005","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2016.05.007_bib43","doi-asserted-by":"crossref","first-page":"e2814","DOI":"10.1371\/journal.pntd.0002814","article-title":"Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation","volume":"8","author":"Yamashita","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"issue":"1","key":"10.1016\/j.toxicon.2016.05.007_bib44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/00001721-200401000-00008","article-title":"Venous and arterial thrombosis in rat models: dissociation of the antithrombotic effects of glycosaminoglycans","volume":"15","author":"Zancan","year":"2004","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"10.1016\/j.toxicon.2016.05.007_bib45","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000092416","article-title":"Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule","volume":"34","author":"Zingali","year":"2005","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"10.1016\/j.toxicon.2016.05.007_bib46","doi-asserted-by":"crossref","first-page":"10794","DOI":"10.1021\/bi00091a034","article-title":"Bothrojaracin, a new thrombin inhibitor isolated from Bothrops jararaca venom: characterization and mechanism of thrombin inhibition","volume":"32","author":"Zingali","year":"1993","journal-title":"Biochemistry"}],"container-title":["Toxicon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010116301362?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010116301362?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T20:40:26Z","timestamp":1655844026000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041010116301362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":46,"alternative-id":["S0041010116301362"],"URL":"https:\/\/doi.org\/10.1016\/j.toxicon.2016.05.007","relation":{},"ISSN":["0041-0101"],"issn-type":[{"type":"print","value":"0041-0101"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exploiting the antithrombotic effect of the (pro)thrombin inhibitor bothrojaracin","name":"articletitle","label":"Article Title"},{"value":"Toxicon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxicon.2016.05.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}