APRR4 Antibody

PAR4 Antibody Definition and Biological Context

PAR4 antibodies target Protease-Activated Receptor 4, a G protein-coupled receptor critical for thrombin-mediated platelet activation . These antibodies fall into two functional categories:

• Blocking antibodies: Inhibit PAR4 activation (e.g., mAb-RC3)

• Detection antibodies: Identify PAR4 expression (e.g., APR-034)

PAR4 contains an extracellular N-terminal domain with a thrombin cleavage site (residues L47–K49) essential for receptor activation .

Key antibody features:

Mechanism of Action in Thrombosis

PAR4 antibodies exert antithrombotic effects through:

1. Thrombin cleavage inhibition: mAb-RC3 prevents thrombin from activating PAR4, reducing platelet aggregation by 50% at 3.2–4.3 µg/mL .

2. Procoagulant activity suppression: Reduces phosphatidylserine exposure by 80% in human blood under shear stress .

3. Genotype-independent efficacy: Equally effective against Ala120 and Thr120 PAR4 variants (IC₅₀ 4.3 vs 3.2 µg/mL) .

Research-Grade PAR4 Antibodies

Three monoclonal antibodies developed against PAR4 extracellular domain:

These enable monitoring of PAR4 activation states in platelets and other cells .

Clinical Relevance

mAb-RC3 demonstrates superior therapeutic potential:

• Ex vivo thrombosis model: Reduces fibrin formation by 60% and thrombus size by 45%

• Safety profile: No bleeding complications observed at antithrombotic doses

• Advantage over small molecules: Maintains efficacy across PAR4 genotypes (Thr120 variant present in 20–80% population)

Future Directions

1. Phase I trials for PAR4-blocking antibodies (pending FDA approval)

2. Combination therapies with P2Y₁₂ inhibitors

3. Biomarker development for thrombotic risk stratification