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Design and Evaluation of Heterobivalent PAR1-PAR2 Ligands as Antagonists of Calcium Mobilization. ACS Med Chem Lett 2019 Jan 10;10(1):121-126



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Pubmed Central ID




Scopus ID

2-s2.0-85058668129 (requires institutional sign-in at Scopus site)   9 Citations


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.

Author List

Majewski MW, Gandhi DM, Rosas R Jr, Kodali R, Arnold LA, Dockendorff C


Alexander (Leggy) Arnold PhD Professor in the Chemistry & Biochemistry department at University of Wisconsin - Milwaukee
Christopher Dockendorff PhD Assistant Professor, Organic and Medicinal Chemistry in the Chemistry department at Marquette University