A long-half-life, high-affinity P-selectin inhibitor
PL Gross - Blood, The Journal of the American Society of …, 2021 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2021•ashpublications.org
In this issue ofBlood, Wong et al describe the synthesis and properties of P-G6, a pegylated
glycomimetic of the N terminus of P-selectin glycoprotein ligand (PSGL-1), which inhibits the
P-selectin–PSGL-1 interaction. 1 Consistent with this blockade, P-G6 attenuated human and
mouse platelet– monocyte and platelet– neutrophil aggregation in vitro and blocked platelet–
leukocyte interactions in vivo. Pegylation endowed P-G6 with a half-life of 16 hours in mice,
and a single IV dose of P-G6 inhibited electrolytic injury– induced venous thrombosis in a …
glycomimetic of the N terminus of P-selectin glycoprotein ligand (PSGL-1), which inhibits the
P-selectin–PSGL-1 interaction. 1 Consistent with this blockade, P-G6 attenuated human and
mouse platelet– monocyte and platelet– neutrophil aggregation in vitro and blocked platelet–
leukocyte interactions in vivo. Pegylation endowed P-G6 with a half-life of 16 hours in mice,
and a single IV dose of P-G6 inhibited electrolytic injury– induced venous thrombosis in a …
In this issue ofBlood, Wong et al describe the synthesis and properties of P-G6, a pegylated glycomimetic of the N terminus of P-selectin glycoprotein ligand (PSGL-1), which inhibits the P-selectin–PSGL-1 interaction. 1 Consistent with this blockade, P-G6 attenuated human and mouse platelet– monocyte and platelet– neutrophil aggregation in vitro and blocked platelet– leukocyte interactions in vivo. Pegylation endowed P-G6 with a half-life of 16 hours in mice, and a single IV dose of P-G6 inhibited electrolytic injury– induced venous thrombosis in a murine model to the same extent as enoxaparin. Whereas enoxaparin prolonged the bleeding time after tail tip amputation, P-G6 did not. Based on these fi ndings, the authors consider P-G6 an attractive candidate for prevention and treatment of venous thromboembolism (VTE).
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