Faculty Collaboration Database

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

Date

01/19/2019

Pubmed ID

30655958

Pubmed Central ID

PMC6331166

DOI

10.1021/acsmedchemlett.8b00538

Scopus ID

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

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.

Author List

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

Authors

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