Introduction: Anticoagulation without
bleeding is an ideal goal in treating
thrombosis, however, this goal has not been achieved. All current
anticoagulants are associated with significant
bleeding which limits their safe use. Genetic and pharmacological findings indicate that
factor XIa is a key player in
thrombosis, yet it is a relatively marginal one in hemostasis. Thus,
factor XIa and its
zymogen offer a unique opportunity to develop
anticoagulants with low
bleeding risk.Areas covered: A survey of patent literature has retrieved more than 50 patents on the discovery of novel
therapeutics targeting
factor XI(a) since 2016. Small molecules,
monoclonal antibodies,
oligonucleotides, and
polypeptides have been developed to inhibit
factor XI(a). Many inhibitors are in early development and few have been evaluated in clinical trials.Expert opinion:
Factor XI(a) is being actively pursued as a
drug target for the development of effective and safer
anticoagulants. Although many patents claiming
factor XI(a) inhibitors were filed prior to 2016, recent literature reveals a moderately declining trend. Nevertheless, more agents have entered different levels of clinical trials. These agents exploit diverse mechanistic strategies for inhibition. Although further development is warranted, reaching one or more of these agents to the clinic will transform the anticoagulation
therapy.