A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis

Blood. 2021 Sep 30;138(13):1182-1193. doi: 10.1182/blood.2020009428.


Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Hemostasis / drug effects
  • Humans
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / pharmacology
  • Membrane Glycoproteins / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation / drug effects
  • P-Selectin / antagonists & inhibitors*
  • P-Selectin / metabolism
  • Platelet Aggregation / drug effects
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • Thrombosis / drug therapy*
  • Thrombosis / metabolism


  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Polyethylene Glycols