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A Pharmacodynamic Study of CN-218, a Novel Antiplatelet and Antithrombotic Agent Primarily Targeting the P2Y12 Receptor

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Drugs inhibiting the platelet P2Y12 receptor, such as clopidogrel and prasugrel, are potent antithrombotic agents and are widely used in cardiovascular disease. However, the adverse effects of these drugs have limited their clinical use. For example, clopidogrel resistance occurs in approximately one third of patients, while prasugrel increases the risk of major bleeding. Therefore, new generations of such drugs are of clinical interest.


In this study, the pharmacodynamics of a new P2Y12 antagonist, CN-218, was compared with that of clopidogrel and prasugrel in rats and mice. The differences between CN-218 and clopidogrel include deuteration of the 7-position methyl carboxylate and the introduction of cinnamate in the 2-position of thiophene.


CN-218 had an antiaggregatory efficacy that was at least five times more potent than that of clopidogrel but not as potent as that of prasugrel. It had a significant impact on activated partial thromboplastin time (APTT), whereby the APTT of CN-218-treated rats was approximately 9 s longer than that of the vehicle- or clopidogrel-treated group, while it had no impact on prothrombin time (PT) in rats. CN-218 had a similar potent antithrombotic effect to that of prasugrel and clopidogrel and also reduced the risk of bleeding compared to prasugrel.


CN-218 may be a promising antithrombotic agent, with potent antiplatelet and significant anticoagulant activity, as well as a lower risk of bleeding compared to clopidogrel and prasugrel.

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We thank Conn Hastings, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.


This work was supported by the Health and Family Planning Commission of Jilin Province (No. 2017 J055) and the Education Department of Jilin Province (No. JJKH20190009KJ).

Author information

Conceptualization of study, Xia Cao and Jinkai Gu; experimental design, Xiaohua Li, Peng Liu, and Zhiping Xu; performed the experiments, Xiaohua Li, Peng Liu, Zhiping Xu, Dong Sun, Yujia Miao, and Jujin Zhang; data analysis and interpretation, Xiaohua Li, Peng Liu, and Xia Cao; funding acquisition and supervision, Xia Cao; original manuscript draft preparation, Xiaohua Li; reviewing and editing the manuscript, Xiaohua Li. All authors have read and approved the final manuscript.

Correspondence to Xia Cao.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Animal Experiment Committee of Jilin University. Experimental mice and rats were housed with 12/12 h dark/light cycles and standard food and water under specific sterile (SPF) conditions. All mice and rats were provided with anesthesia and postoperative care.

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Li, X., Liu, P., Xu, Z. et al. A Pharmacodynamic Study of CN-218, a Novel Antiplatelet and Antithrombotic Agent Primarily Targeting the P2Y12 Receptor. Cardiovasc Drugs Ther (2020). https://doi.org/10.1007/s10557-019-06930-9

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  • P2Y12 receptor antagonist
  • Platelet
  • Clopidogrel
  • Prasugrel
  • Site-specific deuterium
  • Cinnamate