SV预防血栓药理学作用及其机制研究探讨

Study on the pharmacological effect and mechanism of SV in prevention of thrombus

血栓栓塞性疾病是人类首要致死病因,临床预防血栓药物均存在出血危险。选择性的内源性凝血途径抑制剂已成为低出血倾向预防血栓药物研发的重点方向。SV是以天然岩藻糖化糖胺聚糖(FG)为先导化合物经结构优化获得的选择性内源性凝血因子Xase抑制剂(IC50=30 nm),其抑制内源性凝血活性与依诺肝素相当,在等效抗凝血剂量的倍数剂量下出血倾向显著降低。本文探讨低出血倾向的SV预防血栓药理学作用及其机制,为选择性Xase抑制剂及其新药发现研究提供参考依据。

Thromboembolic diseases are the leading cause of death in humans, and there is a risk of bleeding in clinical thromboprophylaxis drugs. Selective endogenous coagulation pathway inhibitors have become the focus of research and development of thromboprophylaxis drugs with low hemorrhagic tendency. SV is a selective endogenous coagulation factor Xase inhibitor(IC50=30 nm) obtained by structural optimization with natural fucosylated glycosaminoglycan(FG) as the lead compound. Its inhibiting endogenous coagulation activity is comparable to enoxaparin. At multiple doses of equivalent anticoagulation dose, the bleeding tendency is significantly reduced. In this paper, the pharmacological effect and mechanism of low hemorrhagic tendency of SV in preventing thrombosis were discussed, which provided a reference for the research of selective Xase inhibitors and discovery of new drugs.