CGS 21680 is a Selective Adenosine A2A Receptor Agonist

CGS21680 significantly upregulates CD39 and CD73 expression. And the compound accelerates the adenosine triphosphate (ATP) hydrolysis and adenosine generation. The inhibitor (10 nM) alone shows only small survival activity, but the activity is significantly enhanced by the addition of a phosphodiesterase inhibitor, IBMX.

CGS21680 (1 mg/kg/i.p.) intervention promotes the development of EAN. CGS21680 exacerbates experimental autoimmune neuritis in Lewis rats induced with bovine peripheral myelin. The exacerbation is accompanied with reduced CD4+ Foxp3+ T cells, increased CD4+ CXCR5+ T cells, B cells, dendritic cells and antigen-specific autoantibodies, which is possibly due to the inhibition of IL-2 induced by CGS21680. CGS21680 (0.1 mg/kg, i.p.) transiently increases heart frequency but does not modify blood pressure of rat.

CGS 21680 is a selective adenosine A2A receptor agonist, with a Ki of 27 nM.

Adenosine and CGS21680 promote CD39 and CD73 by upregulating E2F-1 or CREB, constituting the CD39/CD73/adenosine pathway. In addition, adenosine and CGS21680 exhibit as two indirect activators of CD39 and CD73 by upregulating E2F-1 and CREB. As the specific adenosine A2A receptor agonist, CGS21680 divides adenosine receptor A2A from A2B based on different affinities.

Also, CGS21680 upregulates p-E2F-1; however, it does not affect E2F-1 expression.  Furthermore, the amount of AMP, the hydrolysate of ATP, kept increasing until 40 min post-ATP treatment and the CGS21680-treated cells exhibited significant differences before this time point when compared with the untreated cells (P<0.05).

CGS21680 accelerates the presence of the adenosine cycle.


Komaki S, et al. Trk and cAMP-dependent survival activity of adenosine A(2A) agonist CGS21680 on rat motoneurons in culture. Neurosci Lett. 2012 Jul 26;522(1):21-4.