MRS2279 diammonium is a selective and high affinity P2Y1 receptor antagonist, with a Ki value of 2.5 nM and an IC50 value of 51.6 nM. MRS2279 diammonium competitively inhibits ADP-promoted platelet aggregation with an pKb value of 8.05.
MRS2279 diammonium antagonizes 2-MeSADP-stimulated inositol phosphate formation in turkey erythrocyte membranes with a pKb value of 7.75[2]. MRS2279 diammonium shows high affinity competitive antagonism to human P2Y1 receptor with a pKb value of 8.10 in 1321N1 human astrocytoma cells[2].MRS2279 diammonium shows specific effect for the P2Y1 receptor, but shows no effect on activation of the human P2Y2, P2Y4, P2Y6, or P2Y11 receptors by their cognate agonists[2]. MRS2279 diammonium shows no ability to block the capacity of ADP to act through the Gi/adenylyl cyclase linked P2Y receptor of platelets to inhibit cyclic AMP accumulation[2].
MRS2279 diammonium (2 μL, 1 nM; intracerebroventricular injection; 30 min prior to mechanical ventilation) reduces mouse brain injury induced by mechanical ventilation in high-pressure ventilation mice[3].
References:
[1]. Nandanan E, et al. Synthesis, biological activity, and molecular modeling of ribose-modified deoxyadenosine bisphosphate analogues as P2Y(1) receptor ligands. J Med Chem. 2000;43(5):829-842.
[2]. Boyer JL, et al, Ravi RG, Jacobson KA, Harden TK. 2-Chloro N(6)-metl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate is a selective high affinity P2Y(1) receptor antagonist. Br J Pharmacol. 2002;135(8):2004-2010.
[3]. Wei W, et al. Mechanical ventilation induces lung and brain injury through ATP production, P2Y1 receptor activation and dopamine release. Bioengineered. 2022 Feb;13(2):2346-2359.