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Updated: Jan 16, 2026

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Protease-Activated Receptor 4 (PAR4)-Tethered Ligand Antagonists Demonstrate Thrombin Liability
Emma M Webb1, Jackson B Cassada1, Heidi E Hamm1,2
1Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6600, United States.
Abstract:
The Hamm laboratory recently published a cohort of PAR4 antagonists that were effective against the tethered ligand activation of PAR4. These compounds were generated from an ultralarge virtual screen using a homology model of PAR4. Upon further investigation, it appears the protease-activated receptor antagonists highlighted in this work have some thrombin liability. The Hamm laboratory further characterized the activity of these compounds using various methods, including a fluorescent thrombin activity assay, a chromogenic thrombin activity assay, and flow cytometry assays. We conclude that they do indeed antagonize PAR4, but thrombin is an additional target.
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