Coagulation factor XI (FXI) (FXI)

Coagulation factor XI (FXI) is a plasma serine protease zymogen that plays a pivotal role in the intrinsic pathway of the blood coagulation cascade (UniProt P03951). It circulates as a homodimer, with each subunit comprising four apple domains (A1-A4) and a C-terminal catalytic domain. The A2 domain is specifically involved in the binding of Factor IX and Factor XIIa, while the catalytic domain contains the active site responsible for proteolysis (PMID: 33035324). Upon activation to FXIa, it activates Factor IX, leading to the amplification of thrombin generation and the stabilization of fibrin clots. FXI has emerged as a high-priority therapeutic target because its inhibition effectively prevents thrombosis with a minimal impact on primary hemostasis, offering a wider safety margin than traditional anticoagulants (PMID: 34788507). Pharmacological strategies include small molecules like milvexian that bind the catalytic site, monoclonal antibodies like abelacimab that target the catalytic domain, and antisense oligonucleotides like fesomersen that reduce hepatic synthesis (ClinicalTrials.gov). This target is particularly relevant for patients who require anticoagulation but are at high risk for bleeding complications, such as those with end-stage renal disease or atrial fibrillation.

Other names

Plasma thromboplastin antecedentPTAF11Coagulation factor 11

Inhibition of the enzymatic activity of activated Factor XI (FXIa) or prevention of its activation by targeting the catalytic domain or allosterically modulating apple domains (A1-A4) (PMID: 33035324).