Journal article
Novel Irreversible Agonists Acting at the A1 Adenosine Receptor
M Jörg, A Glukhova, A Abdul-Ridha, EA Vecchio, ATN Nguyen, PM Sexton, PJ White, LT May, A Christopoulos, PJ Scammells
Journal of Medicinal Chemistry | AMER CHEMICAL SOC | Published : 2016
Abstract
The A1 adenosine receptor (A1AR) is an important G protein-coupled receptor that regulates a range of physiological functions. Herein we report the discovery of novel irreversible agonists acting at the A1AR, which have the potential to serve as useful research tools for studying receptor structure and function. A series of novel adenosine derivatives bearing electrophilic substituents was synthesized, and four compounds, 8b, 15a, 15b, and 15d, were shown to possess similar potency and efficacy to the reference high efficacy agonist, NECA, in an assay of ERK1/2 phosphorylation assay. Insensitivity to antagonist addition in a real-time, label-free, xCELLigence assay was subsequently used to i..
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Funding Acknowledgements
We thank Dr. Michael Crouch (TGR Biosciences) for generously providing the ERK1/2 phosphorylation assay kit. This work was funded by Project Grants APP1084246 and APP1084487 of the National Health and Medical Research Council of Australia (NHMRC). A.C. is a Senior Principal Research Fellow, and P.M.S. a Principal Research Fellow, of the NHMRC.