Document Type



Medicine and Health Sciences


The Gi-coupled A3 adenosine receptor (A3AR) mediates anti-inflammatory, anticancer and anti-ischemic protective effects. The receptor is overexpressed in inflammatory and cancer cells, while low expression is found in normal cells, rendering the A3AR as a potential therapeutic target. Highly selective A3AR agonists have been synthesized and molecular recognition in the binding site has been characterized. The present review summarizes preclinical and clinical human studies demonstrating that A3AR agonists induce specific anti-inflammatory and anticancer effects via a molecular mechanism that entails modulation of the Wnt and the NF-κB signal transduction pathways. Currently, A3AR agonists are being developed for the treatment of inflammatory diseases including rheumatoid arthritis and psoriasis; ophthalmic diseases such as dry eye syndrome and glaucoma; liver diseases such as hepatocellular carcinoma and hepatitis.


Drug Discov Today. Author manuscript; available in PMC 2013 April 1. Published in final edited form as: Drug Discov Today. 2012 April; 17(7-8): 359–366. Published online 2011 October 19. doi: 10.1016/j.drudis.2011.10.007 PMCID: PMC3289754 NIHMSID: NIHMS332917