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Updated: Jan 30, 2026

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Design and Evaluation of Heterobivalent PAR1-PAR2 Ligands as Antagonists of Calcium Mobilization
Mark W Majewski1, Disha M Gandhi1, Ricardo Rosas1
1Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, Wisconsin 53201-1881, United States.
Abstract:
A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1-PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders.
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