Allosteric modulation of adenosine receptors

作者：Goblyos Aniko; IJzerman Ad P^*

来源：Biochimica et Biophysica Acta-Biomembranes, 2011, 1808(5): 1309-1318.

DOI：10.1016/j.bbamem.2010.06.013

• Adenosine receptor
• Allosteric modulation
• Hybrid allo/orthosteric ligand
• PD81,723
• LUF5485
• LUF6000
• LUF6096

Allosteric ligands for G protein-coupled receptors (GPCRs) may alter receptor conformations induced by an orthosteric ligand. These modulators can thus fine-tune classical pharmacological responses. In this review we will describe efforts to synthesize and characterize allosteric modulators for one particular GPCR subfamily, the adenosine receptors. There are four subtypes of these receptors: A(1), A(2A), A(2B) and A(3). Allosteric enhancers for the adenosine A(1) receptor may have anti-arrythmic and anti-lipolytic activity. They may also act as analgesics and neuroprotective agents. A(3) allosteric enhancers are thought to be beneficial in ischemic conditions or as antitumor agents. We will summarize recent developments regarding the medicinal chemistry of such compounds. Most data have been and are published about the adenosine A(1) and A3 receptor, whereas limited or no information is available for the A(2A) and A(2B) receptor, respectively. Receptor mutation studies are also discussed, as they may shed light on the localization of the allosteric binding sites. This article is part of a Special Issue entitled: "Adenosine Receptors".

• 出版日期2011-5