Paper2-[3-[2-(4,5-diphenyl-2-oxazolyl) ethyl] phenoxy] acetic acid (BMY 42393): A new, structurally-novel prostacyclin partial agonist: 1) inhibition of platelet aggregation and mechanism of action

Add time:09/04/2019    Source:sciencedirect.com

BMY 42393, (2-[3-[2-(4,5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid), is a new prostacyclin partial agonist that inhibited ADP, collagen and thrombin-induced platelet aggregation (IC50 range 0.3 - 2.0 μM). BMY 42393 stimulated platelet adenylate cyclase activity (EC50 = 25 μM), however, the maximal activation was 75–80 % of that observed with maximal iloprost or PGE1. Platelets treated with BMY 42393 showed an elevation of cAMP levels and activation of cAMP-dependent protein kinase. BMY 42393 also inhibited thrombin-induced elevation of intracellular free calcium. BMY 42393 competed for radiolabeled iloprost and PGE1 binding to platelet membranes (IC50: 170 nM and 130 nM, respectively); however, it had little effect on radiolabeled PGE2, PGD2, or SQ 29548 binding. These studies indicate that BMY 42393 is a novel platelet aggregation inhibitor which acts by stimulation of platelet prostacyclin receptors to elevate platelet cAMP levels.

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