Development of P2Y₁₂ Receptor Antagonists for Cardiovascular Diseases

The P2Y₁₂ receptor play an important role in platelet activation, thrombosis, and the pathogenesis of thrombotic diseases, making it a key target for antithrombotic drugs. Ace Therapeutics is actively engaged in providing comprehensive outsourcing services for cardiovascular drug discovery and development. Our mission is to deliver the research expertise required for the advancement of P2Y₁₂ inhibitors, ensuring innovative and effective therapeutic solutions.

The Role of The P2Y₁₂ Receptor in Cardiovascular Diseases

The P2Y₁₂ receptor, a G protein-coupled receptor (GPCR), selectively binds adenosine diphosphate (ADP) and is primarily expressed on platelet surfaces. It plays a pivotal role in hemostasis and thrombosis, making it a critical target for antiplatelet therapy. P2Y₁₂ receptor blockers are widely used in clinical settings to prevent thrombosis in patients with acute coronary syndromes (ACS), ischemic stroke, and those undergoing percutaneous coronary intervention (PCI).

Fig. 1 Mechanism of action and metabolism of P2Y₁₂ receptor inhibitors. (Nappi F, 2024)

Current Status of P2Y₁₂ Receptor Antagonist Development

P2Y₁₂ receptor antagonists are a class of drugs that target platelet P2Y₁₂ receptors, inhibiting ADP-induced platelet aggregation. These agents are primarily used in the treatment of acute coronary syndrome, coronary artery restenosis, myocardial infarction, acute ischemic stroke, and related conditions.

P2Y₁₂ Receptor Antagonists in Development or Approved for the Treatment of Cardiovascular Diseases

Discovery of P2Y₁₂ Receptor Antagonists

Leveraging our expertise and advanced platforms, we are committed to supporting our clients in developing a wide range of P2Y₁₂ receptor antagonists. Our services are designed to accelerate the discovery and optimization of novel therapeutic candidates.

• Small Molecule P2Y₁₂ Receptor Antagonist
  We assist our clients in developing novel small molecule P2Y₁₂ receptor antagonists, as well as dual-action inhibitors that target both the P2Y₁₂ receptor and other platelet activation-associated receptors (e.g., PAR-1).

In Vitro Pharmacodynamic Studies

• Receptor Binding Assay
  We utilize advanced fluorescent labelling techniques to evaluate the binding affinity and inhibition constants of test drugs targeting the P2Y₁₂ receptor. This approach provides precise and reliable data on drug-receptor interactions, enabling the optimization of therapeutic candidates.
• In Vitro Platelet Aggregation Inhibition Assay
  Using platelet rich plasma (PRP) or whole blood, we can assess the inhibitory effects of test drugs on ADP-induced platelet aggregation. By measuring the half-maximal inhibitory concentration (IC₅₀) and maximal inhibition rate, we gain critical insights into the potency and efficacy of antiplatelet agents.

In Vivo Pharmacodynamic Studies

• Effect on Thrombosis
  To meet specific research needs, we can select or develop tailored animal models of thrombosis. These models allow us to evaluate key parameters such as thrombus formation rate, vessel occlusion time, hemodynamic changes, and overall thrombus development, providing a comprehensive understanding of drug efficacy.
• Platelet Function Test
  To ensure the safety of antiplatelet therapies, we can conduct tail vein transection bleeding models to determine whether test drugs increase bleeding tendency, a critical factor in balancing efficacy and safety for clinical applications.
• Effect on Atherosclerosis
  We choose ApoE-/- or LDL-R-/- mice fed a high-fat diet to induce atherosclerosis, creating a robust model to study the effects of P2Y₁₂ receptor antagonists. These studies focus on platelet-mediated inflammation and atherosclerosis progression, offering valuable insights into the therapeutic potential of antiplatelet agents.

Ace Therapeutics is a company that provides outsourcing services of cardiovascular disease research for clients. We provide a full range of technical support and development services for a variety of cardiovascular disease drugs, such as P2Y₁₂ receptor blockers. If you are interested in our services, please do not hesitate to contact us.

1. Nappi F. P2Y₁₂ receptor inhibitor for antiaggregant therapies: from molecular pathway to clinical application. Int J Mol Sci. 2024, 25(14):7575.