Scholarlink

Purpose <p>Patients with acute coronary syndrome (ACS) require rapid and potent antiplatelet therapy during percutaneous coronary intervention (PCI). Current first-line P2Y₁₂ inhibitors are limited by delayed efficacy or an ultrashort half-life. This study aims to characterize the metabolism and pharmacodynamics of HY-022619, a disodium phosphate ester salt of ticagrelor, to provide a theoretical basis for its clinical use in peri-PCI antithrombotic therapy.</p> Methods <p>The inhibitory activity of HY-022619 against the P2Y₁₂ receptor and ADP-induced platelet aggregation was evaluated <i>in vitro</i>. Molecular docking was performed to compare its receptor-binding mode with ticagrelor. Metabolic stability was assessed in whole blood, liver microsomes, and using recombinant enzymes. Pharmacodynamic profiles were investigated in rats and beagle dogs, with additional assessments of metabolic conversion and bleeding time in dogs.</p> Results <p>HY-022619 showed 22-fold greater P2Y₁₂ receptor inhibition and 15-fold stronger suppression of platelet aggregation than ticagrelor. Molecular docking revealed that enhanced activity was due to an additional salt bridge. HY-022619 remained stable in human and non-rodent whole blood (half-life &gt; 60&#xa0;min) and was primarily hydrolysed to ticagrelor in the liver by CES1 and CES2. In rats, intravenous administration produced rapid, dose-dependent platelet inhibition within 5&#xa0;min. In dogs, HY-022619 acted rapidly with efficacy peaking at the end of infusion. It converted completely to ticagrelor within 5&#xa0;min post-infusion, maintaining antiplatelet effects for 6&#xa0;h, without significantly prolonging bleeding time compared to ticagrelor.</p> Conclusion <p>HY-022619 demonstrates rapid, potent, and sustained antiplatelet effects, supporting its potential clinical application.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

In vitro and ex vivo Pharmacological Profile of HY-022619, a Novel Intravenous P2Y12 Receptor Antagonist with Rapid-onset and Sustained Antiplatelet Activity

  • 期刊论文

  • 发表日期：

    2026年4月8日

查看全文
  • Jiajia Mo,
  • Emily M. He,
  • Yan Zhao,
  • Li Shao,
  • Shaoyun Yue,
  • Yanmei Xie,
  • Shiqi Wu,
  • Jianxun He,
  • Yi Zou,
  • Zhaoxing Chu,
  • Guangwei He,
  • Yungen Xu

摘要

Purpose

Patients with acute coronary syndrome (ACS) require rapid and potent antiplatelet therapy during percutaneous coronary intervention (PCI). Current first-line P2Y₁₂ inhibitors are limited by delayed efficacy or an ultrashort half-life. This study aims to characterize the metabolism and pharmacodynamics of HY-022619, a disodium phosphate ester salt of ticagrelor, to provide a theoretical basis for its clinical use in peri-PCI antithrombotic therapy.

Methods

The inhibitory activity of HY-022619 against the P2Y₁₂ receptor and ADP-induced platelet aggregation was evaluated in vitro. Molecular docking was performed to compare its receptor-binding mode with ticagrelor. Metabolic stability was assessed in whole blood, liver microsomes, and using recombinant enzymes. Pharmacodynamic profiles were investigated in rats and beagle dogs, with additional assessments of metabolic conversion and bleeding time in dogs.

Results

HY-022619 showed 22-fold greater P2Y₁₂ receptor inhibition and 15-fold stronger suppression of platelet aggregation than ticagrelor. Molecular docking revealed that enhanced activity was due to an additional salt bridge. HY-022619 remained stable in human and non-rodent whole blood (half-life > 60 min) and was primarily hydrolysed to ticagrelor in the liver by CES1 and CES2. In rats, intravenous administration produced rapid, dose-dependent platelet inhibition within 5 min. In dogs, HY-022619 acted rapidly with efficacy peaking at the end of infusion. It converted completely to ticagrelor within 5 min post-infusion, maintaining antiplatelet effects for 6 h, without significantly prolonging bleeding time compared to ticagrelor.

Conclusion

HY-022619 demonstrates rapid, potent, and sustained antiplatelet effects, supporting its potential clinical application.

Graphical Abstract