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FXIa primarily catalyzes factor IX activation to factor IXa, which subsequently activates factor X to factor Xa in the common coagulation pathway. Growing evidence suggests that FXIa plays an important role in thrombosis with a relatively limited contribution to hemostasis. Therefore, inhibitors targeting factor XI (FXI)\/FXIa system have emerged as a paradigm\u2010shifting strategy so as to develop a new generation of anticoagulants to effectively prevent and\/or treat thromboembolic diseases without the life\u2010threatening risk of internal bleeding. Several inhibitors of FXI\/FXIa proteins have been discovered or designed over the last decade including polypeptides, active site peptidomimetic inhibitors, allosteric inhibitors, antibodies, and aptamers. Antisense oligonucleotides (ASOs), which ultimately reduce the hepatic biosynthesis of FXI, have also been introduced. A phase II study, which included patients undergoing elective primary unilateral total knee arthroplasty, revealed that a specific FXI ASO effectively protects patients against venous thrombosis with a relatively limited risk of bleeding. Initial findings have also demonstrated the potential of FXI\/FXIa inhibitors in sepsis, listeriosis, and arterial hypertension. This review highlights various chemical, biochemical, and pharmacological aspects of FXI\/FXIa inhibitors with the goal of advancing their development toward clinical use.<\/jats:p>","DOI":"10.1002\/med.21503","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T08:34:53Z","timestamp":1525422893000},"page":"1974-2023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Recent advances in the discovery and development of factor XI\/XIa inhibitors"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-2662","authenticated-orcid":false,"given":"Rami A.","family":"Al\u2010Horani","sequence":"first","affiliation":[{"name":"Division of Basic Pharmaceutical Sciences, College of Pharmacy Xavier University of Louisiana  New Orleans LA 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