{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:20:49Z","timestamp":1792092049396,"version":"4.4.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973221"],"award-info":[{"award-number":["81973221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002857","name":"China Pharmaceutical University","doi-asserted-by":"publisher","award":["CPU2018GY15"],"award-info":[{"award-number":["CPU2018GY15"]}],"id":[{"id":"10.13039\/501100002857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011360","name":"State Key Laboratory of Natural Medicines","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.bioorg.2023.106951","type":"journal-article","created":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T19:05:11Z","timestamp":1698606311000},"page":"106951","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis"],"prefix":"10.1016","volume":"142","author":[{"given":"Feilong","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.bioorg.2023.106951_b0005","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.115.306841","article-title":"Global burden of thrombosis: epidemiologic aspects","volume":"118","author":"Wendelboe","year":"2016","journal-title":"Circ Res"},{"issue":"5","key":"10.1016\/j.bioorg.2023.106951_b0010","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41573-020-0061-0","article-title":"Therapeutic strategies for thrombosis: new targets and approaches","volume":"19","author":"Mackman","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"issue":"1","key":"10.1016\/j.bioorg.2023.106951_b0015","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tcm.2014.09.001","article-title":"Warfarin pharmacogenetics","volume":"25","author":"Johnson","year":"2015","journal-title":"Trends Cardiovasc. Med."},{"issue":"22","key":"10.1016\/j.bioorg.2023.106951_b0020","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1161\/CIRCULATIONAHA.108.832139","article-title":"Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome","volume":"119","author":"Alexander","year":"2009","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.bioorg.2023.106951_b0025","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5811\/westjem.2014.12.22933","article-title":"Anticoagulation drug therapy: a review","volume":"16","author":"Harter","year":"2015","journal-title":"West J Emerg Med"},{"key":"10.1016\/j.bioorg.2023.106951_b0030","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/biomedicines9030262","article-title":"Updates in Anticoagulation Therapy Monitoring","volume":"9","author":"McRae","year":"2021","journal-title":"Biomedicines"},{"issue":"13","key":"10.1016\/j.bioorg.2023.106951_b0035","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1136\/heartjnl-2016-310358","article-title":"Effects of dabigatran according to age in atrial fibrillation","volume":"103","author":"Lauw","year":"2017","journal-title":"Heart"},{"issue":"4","key":"10.1016\/j.bioorg.2023.106951_b0040","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/ehjcvp\/pvy021","article-title":"Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study","volume":"4","author":"Sindet-Pedersen","year":"2018","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"10.1016\/j.bioorg.2023.106951_b0045","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1016\/S0049-3848(16)30363-2","article-title":"Factor XI and factor XII as targets for new anticoagulants","volume":"141","author":"Weitz","year":"2016","journal-title":"Thromb. Res."},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0050","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1160\/TH10-05-0307","article-title":"Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis","volume":"105","author":"Salomon","year":"2011","journal-title":"Thromb Haemost"},{"issue":"8","key":"10.1016\/j.bioorg.2023.106951_b0055","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1182\/blood-2007-10-120139","article-title":"Reduced incidence of ischemic stroke in patients with severe factor XI deficiency","volume":"111","author":"Salomon","year":"2008","journal-title":"Blood"},{"issue":"02","key":"10.1016\/j.bioorg.2023.106951_b0060","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1055\/a-1384-3715","article-title":"Factor XI as a target for new anticoagulants","volume":"41","author":"Fredenburgh","year":"2021","journal-title":"Hamostaseologie"},{"issue":"4","key":"10.1016\/j.bioorg.2023.106951_b0065","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1538-7836.2005.01236.x","article-title":"Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice","volume":"3","author":"Wang","year":"2005","journal-title":"J. Thromb. Haemost."},{"issue":"9","key":"10.1016\/j.bioorg.2023.106951_b0070","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1111\/j.1538-7836.2006.02093.x","article-title":"Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice","volume":"4","author":"Wang","year":"2006","journal-title":"J. Thromb. Haemost."},{"issue":"9","key":"10.1016\/j.bioorg.2023.106951_b0075","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00011-010-0205-5","article-title":"Anti-inflammatory actions of serine protease inhibitors containing the Kunitz domain","volume":"59","author":"Shigetomi","year":"2010","journal-title":"Inflamm Res"},{"issue":"9\u201310","key":"10.1016\/j.bioorg.2023.106951_b0080","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.micinf.2018.01.003","article-title":"Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival","volume":"20","author":"de Magalhaes","year":"2018","journal-title":"Microbes Infect"},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0085","doi-asserted-by":"crossref","first-page":"e32269","DOI":"10.1371\/journal.pone.0032269","article-title":"Antifibrinolytic role of a bee venom serine protease inhibitor that acts as a plasmin inhibitor","volume":"7","author":"Choo","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.bioorg.2023.106951_b0090","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.fsi.2018.05.058","article-title":"Kunitz-type serine protease inhibitor is a novel participator in anti-bacterial and anti-inflammatory responses in Japanese flounder (Paralichthys olivaceus)","volume":"80","author":"Xu","year":"2018","journal-title":"Fish Shellfish Immunol"},{"key":"10.1016\/j.bioorg.2023.106951_b0095","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ijid.2017.10.024","article-title":"Kunitz-type protease inhibitor as a vaccine candidate against schistosomiasis mansoni","volume":"66","author":"Ranasinghe","year":"2018","journal-title":"Int J Infect Dis"},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0100","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/jb\/mvs133","article-title":"P1 and P2' site mutations convert protease nexin-2 from a factor XIa inhibitor to a plasmin inhibitor","volume":"153","author":"Navaneetham","year":"2013","journal-title":"J. Biochem."},{"issue":"43","key":"10.1016\/j.bioorg.2023.106951_b0105","doi-asserted-by":"crossref","first-page":"36165","DOI":"10.1074\/jbc.M504990200","article-title":"Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2","volume":"280","author":"Navaneetham","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bioorg.2023.106951_b0110","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jbiotec.2021.02.016","article-title":"Selection and in vitro and in vivo characterization of a Kunitz protease inhibitor domain of protease nexin 2 variant that inhibits factor XIa without inhibiting plasmin","volume":"330","author":"Eltringham-Smith","year":"2021","journal-title":"J Biotechnol"},{"issue":"8","key":"10.1016\/j.bioorg.2023.106951_b0115","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2146\/ajhp110227","article-title":"Ecallantide for treatment of acute attacks of hereditary angioedema","volume":"69","author":"Martello","year":"2012","journal-title":"Am J Health Syst Pharm"},{"issue":"3","key":"10.1016\/j.bioorg.2023.106951_b0120","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrd3125","article-title":"Ecallantide","volume":"9","author":"Zuraw","year":"2010","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"10.1016\/j.bioorg.2023.106951_b0125","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.anai.2012.12.007","article-title":"Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks","volume":"110","author":"Sheffer","year":"2013","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0130","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2500\/aap.2013.34.3653","article-title":"Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: open-label continuation study","volume":"34","author":"Lumry","year":"2013","journal-title":"Allergy Asthma Proc"},{"issue":"4","key":"10.1016\/j.bioorg.2023.106951_b0135","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/jb\/mvq080","article-title":"Mechanisms and specificity of factor XIa and trypsin inhibition by protease nexin 2 and basic pancreatic trypsin inhibitor","volume":"148","author":"Navaneetham","year":"2010","journal-title":"J Biochem"},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0140","doi-asserted-by":"crossref","first-page":"e490","DOI":"10.1542\/peds.2013-0646","article-title":"Use of ecallantide in pediatric hereditary angioedema","volume":"132","author":"MacGinnitie","year":"2013","journal-title":"Pediatrics"},{"issue":"9","key":"10.1016\/j.bioorg.2023.106951_b0145","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1517\/13543784.15.9.1077","article-title":"The therapeutic potential of a kallikrein inhibitor for treating hereditary angioedema","volume":"15","author":"Levy","year":"2006","journal-title":"Expert Opin Investig Drugs"},{"issue":"3","key":"10.1016\/j.bioorg.2023.106951_b0150","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/ATVBAHA.118.312130","article-title":"Intrinsic pathway of coagulation and thrombosis","volume":"39","author":"Grover","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"10.1016\/j.bioorg.2023.106951_b0155","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18176\/jiaci.0653","article-title":"Treatment of hereditary angioedema","volume":"31","author":"Caballero","year":"2021","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"issue":"6","key":"10.1016\/j.bioorg.2023.106951_b0160","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa0905079","article-title":"Ecallantide for the treatment of acute attacks in hereditary angioedema","volume":"363","author":"Cicardi","year":"2010","journal-title":"N Engl J Med"},{"issue":"3","key":"10.1016\/j.bioorg.2023.106951_b0165","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1473-0502(03)00170-8","article-title":"DX-88 and HAE: a developmental perspective","volume":"29","author":"Williams","year":"2003","journal-title":"Transfus Apher Sci"},{"issue":"24","key":"10.1016\/j.bioorg.2023.106951_b0170","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1016\/j.jacc.2017.09.1085","article-title":"2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American college of cardiology task force on expert consensus decision pathways","volume":"70","author":"Tomaselli","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"10.1016\/j.bioorg.2023.106951_b0175","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jacc.2011.03.031","article-title":"A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study","volume":"58","author":"Fang","year":"2011","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"10.1016\/j.bioorg.2023.106951_b0180","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1056\/NEJMoa1405760","article-title":"Factor XI antisense oligonucleotide for prevention of venous thrombosis","volume":"372","author":"B\u00fcller","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"05","key":"10.1016\/j.bioorg.2023.106951_b0185","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1055\/s-0039-1692439","article-title":"The safety and efficacy of novel agents targeting factors XI and XII in early phase human trials","volume":"45","author":"DeLoughery","year":"2019","journal-title":"Semin. Thromb. Hemost."},{"issue":"2","key":"10.1016\/j.bioorg.2023.106951_b0190","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/jth.15130","article-title":"Dual inhibition of factor XIIa and factor XIa as a therapeutic approach for safe thromboprotection","volume":"19","author":"Demoulin","year":"2021","journal-title":"J. Thromb. Haemost."},{"issue":"13","key":"10.1016\/j.bioorg.2023.106951_b0195","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1182\/blood-2013-12-540872","article-title":"Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits","volume":"123","author":"Yau","year":"2014","journal-title":"Blood"},{"issue":"17","key":"10.1016\/j.bioorg.2023.106951_b0200","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.jacc.2019.08.1028","article-title":"Anticoagulation with an inhibitor of factors XIa and XIIa during cardiopulmonary bypass","volume":"74","author":"Pireaux","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"issue":"9","key":"10.1016\/j.bioorg.2023.106951_b0205","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1182\/blood-2018-11-882993","article-title":"Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms","volume":"133","author":"Jackson","year":"2019","journal-title":"Blood"},{"issue":"20","key":"10.1016\/j.bioorg.2023.106951_b0210","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1182\/blood-2011-10-386185","article-title":"Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis","volume":"119","author":"Tucker","year":"2012","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.bioorg.2023.106951_b0215","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/jth.14642","article-title":"Fondaparinux pentasaccharide reduces sepsis coagulopathy and promotes survival in the baboon model of Escherichia coli sepsis","volume":"18","author":"Keshari","year":"2020","journal-title":"J. Thromb. Haemost."},{"issue":"8","key":"10.1016\/j.bioorg.2023.106951_b0220","first-page":"591","article-title":"A novel protease-activated receptor 1 inhibitor from the leech Whitmania pigra","volume":"17","author":"Ren","year":"2019","journal-title":"Chin J Nat Med"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823006120?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823006120?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:49:06Z","timestamp":1758617346000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206823006120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":44,"alternative-id":["S0045206823006120"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106951","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106951","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"106951"}}