MRS-1706 is a Selective A(2B) Adenosine Receptor Inverse Agonist

The human adenosine A2B receptor belongs to class A G proteincoupled receptors (GPCRs). And previous studies have verified that constitutively active mutant (CAM) human adenosine A2B receptors were identified from a random mutation bank. Additionally, a study from Qilan Li discovered and identified MRS-1706 as a potent and selective adenosine A2B receptor inverse agonist.

Moreover, MRS-1706 exhibited Ki values of 1.39, 112, 157, and 230 nM for human A2B, A2A, A1 and A3 receptors respectively.

Likewise, MRS 1706 is a newly available potent and selective adenosine A2B receptor antagonist. And  the compound allows to differentiate between effects mediated by A2A- and A2B-receptors. In addition, a study showed the concentration of IL-6 in the perfusate as a function of the time of local infusion of NECA (10-4 M) + MRS 1706 (10-5 M) through the dialysis probe. And MRS 1706 in the NECA solution (N = 6) significantly counteracted the NECA-mediated stimulation of IL-6 release.

Since the antagonism of IL-6 release by MRS 1706 is almost complete and MRS 1706 is highly selective for A2B receptors, A2A and A3 receptors are most likely not involved. To conclude, IL-6 increase progressively appears to be mediated through adenosine A2B receptors since it was counteracted by the specific A2B receptor antagonist MRS1706 but not by the specific A1 receptor antagonist DPCPX.

Furthermore, more in vitro and in vivo  experiments need to be carried out.

1. Li Q, et al. J Pharmacol Exp Ther. 2007 Feb;320(2):637-45.

2. Vazquez JF, et al. J Neurochem. 2008 May;105(3):904-9.