Thromboxane (TXA2) activates the T prostanoid (TP) receptor. Prostaglandin E2 (PGE2) activates four E prostanoid (EP) receptors, EP1-4. AH-23848 is a dual antagonist of TP and EP4 receptors. It originally was found to inhibit TXA2-induced platelet aggregation (IC50 = 0.26 μM) and the contraction of human bronchial smooth muscle induced by the TP agonist U-46619. AH-23848 was subsequently demonstrated to impair PGE2-mediated relaxation of piglet saphenous vein by antagonizing the PGE2 receptor EP4. By inhibiting EP4, it likewise suppresses serum-induced cAMP generation, cyclin A synthesis, and the proliferation of fibroblasts, as well as reduces metastasis in a mouse model of metastatic breast cancer.
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