BAY u3405

IC50: 100-170 nM

BAY u3405 is a DP2 receptor antagonist.

The biological effects of prostaglandin D2 (PGD2) are transduced by at least two 7-transmembrane G protein-coupled receptors, designated DP1 and DP2/CRTH2.

In vitro: BAY u3405 showed significant inhibitory effects on the binding of 3H-labeled PGD2 to CRTH2, albeit with much lower potency. BAY u3405 and indomethacin also inhibited PGD2-induced Ca2+ mobilization in CRTH2 transfectants to almost the same extent. However, indomethacin but not BAY u3405 was confirmed as an agonist of Ca2+ mobilization at concentrations greater than 10 nM [1].

In vivo: For rat with splanchnic artery occlusion shock, administration of BAY u3405 at 30 mg/kg i.v. could significantly increase the survival time and survival rate, improve mean arterial blood pressure, reduce the plasma levels of myocardial depressant factor, partially restore macrophage phagocytosis and lower MPO activity in both the ileum and the lung [2].

Clinical trial: Twelve adult asthmatics were studied in a randomized, double-blind, placebo-controlled study. Three subjects were withdrawn from the evaluation. The Dmin value of 0.533 U after the BAY u3405 treatment was significantly greater than that of 0.135 U after the placebo treatment. There were no safety concerns in either treatment group [3].

References:
[1] Sugimoto, H. ,Shichijo, M.,Iino, T., et al. An orally bioavailable small molecule antagonist of CRTH2, Ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro. Journal of Pharmacology and Experimental Therapeutics 305, 347-352 (2003).
[2] Canale P, Squadrito F, Altavilla D, Ioculano M, Campo GM, Squadrito G, Urna G, Sardella A, Caputi AP.  Beneficial effects of BAY u3405, a novel thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock. Pharmacology. 1994 Dec;49(6):376-85.
[3] Aizawa H, Shigyo M, Nogami H, Hirose T, Hara N. BAY u3405, a thromboxane A2 antagonist, reduces bronchial hyperresponsiveness in asthmatics. Chest. 1996 Feb;109(2):338-42.