MRS2179 is a competitive purinergic P2Y1 receptor antagonist (Kb = 102 nM).1 It is selective for P2Y1 over P2Y2, P2Y4, P2Y6, P2Y12, and P2Y13, as well as P2X1-4, 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)