Factor XIa Inhibitors in Anticoagulation Therapy: Recent Advances and Perspectives

Factor XIa (FXIa) in the intrinsic pathway of the coagulation process has been proven to be an effective and safe target for anticoagulant discovery with limited or no bleeding. Numerous small-molecule FXIa inhibitors (SMFIs) with various scaffolds have been identified in the early stages of drug discovery. They have served as the foundation for the recent discovery of additional promising SMFIs with improved potency, selectivity, and pharmacokinetic profiles, some of which have entered clinical trials for the treatment of thrombosis. After reviewing the coagulation process and structure of FXIa, this perspective discusses the rational or structure-based design, discovery, structure-activity relationships, and development of SMFIs disclosed in recent years. Strategies for identifying more selective and druggable SMFIs are provided, paving the way for the design and discovery of more useful SMFIs for anticoagulation therapy.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Peer-reviewed pharmacology and drug-development research relevant to antithrombotic agents and leech-derived compounds. Indexed in PubMed and verified against the NCBI record.

Explore how this research connects to clinical practice

More peer-reviewed studies in Drug Development.

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• Medicinal Leech Genome Assembly — Anticoagulant Gene Catalog — Kvist et al. (2020)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• HIRUDOTHERAPY IN PRESBYACUZIS PRAECOX IN CLEAN-UP WORKERS AFTER THE CHORNOBYL ACCIDENT DURING THE POST-CATASTROPHE YEARS — Zabolotnyi D, Mishchanchuk N (2019)
• [Hirudo medicinalis-leech applications in plastic and reconstructive microsurgery--a literature review] — Knobloch K et al. (2007)
• Recombinant hirudin in clinical practice: focus on lepirudin — Greinacher A, Lubenow N (2001)
• In-vitro antileishmanial potential of peptide drug hirudin — Khan H et al. (2017)
• Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines — Garcia DA, Baglin TP, Weitz JI, Samama MM (2012)
• Direct thrombin inhibitors — Lee CJ, Ansell JE (2011)
• Updates on Use and Monitoring of Direct Thrombin Inhibitors — Navaei A et al. (2026)

Browse all ASH-analysed research →