MRS2179 (ammonium salt hydrate)

MRS2179 is a competitive purinergic P2Y₁ receptor antagonist (K_b = 102 nM).¹ It is selective for P2Y₁ over P2Y₂, P2Y₄, P2Y₆, P2Y₁₂, and P2Y₁₃, as well as P2X_1-4, receptors at 10 µM.^2,3 MRS2179 reduces phospholipase C (PLC) activity induced by the P2Y receptor agonist 2-methylthioadenosine diphosphate with an IC₅₀ value of 331 nM in turkey erythrocyte membranes that endogenously express high levels of the P2Y₁ receptor.¹ It inhibits platelet shape change and aggregation induced by ADP in washed isolated human platelets when used at a concentration of 10 µM.⁴ MRS2179 (50 mg/kg, i.v.) prolongs the length of tail bleeding time in mice, as well as decreases platelet thrombus formation in a mouse model of iron chloride-induced arterial thrombosis.^4,5

1.Nandanan, E., Camaioni, E., Jang, S.-Y., et al.Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonistsJ. Med. Chem.42(9)1625-1638(1999) 2.von KÜgelgen, I.Pharmacological profiles of cloned mammalian P2Y-receptor subtypesPharmacol. Ther.110(3)415-432(2006) 3.Brown, S.G., King, B.F., Kim, Y.-C., et al.Activity of novel adenine nucleotide derivatives as agonists and antagonists at recombinant rat P2X receptorsDrug Dev. Res.49(4)253-259(2000) 4.Tovar, C., Higgins, B., Deo, D.D., et al.Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapyCell Cycle9(16)3364-3375(2010) 5.Lenain, N., Freund, M., LÉon, C., et al.Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonistJ. Thromb. Haemost.1(6)1144-1149(2003)