Description
U-46619 is a stable analog of the endoperoxide PGH
2, and a TP receptor agonist. It exhibits properties similar to TXA
2, causing platelet shape change, aggregation, and contraction of vascular smooth muscle. Mean EC
50 values for shape change in human, rat, and rabbit platelets are 4.8, 6.0, and 7.3 nM respectively, and for aggregation, are 82, 145, and 65 nM, respectively. U-46619 glycine methyl ester contains a modification at the C-1 position of U-46619 that may uniquely alter its binding properties to the TP receptor or any of the PGH
2-
metabolizing enzymes. As a stable PGH
2 analog, it could therefore be a useful tool to explore the inhibition of various enzymes in the arachidonic acid metabolic pathway. U-46619 glycine methyl ester may also serve as a lipophilic prodrug form of U-46619 that will alter its distribution and pharmacokinetic properties. There are no published reports on the biological activity of U-46619 glycine methyl ester.
References
[1] R.A. COLEMAN. COMPARISON OF THE ACTIONS OF U-46619, A PROSTAGLANDIN H2-ANALOGUE, WITH THOSE OF PROSTAGLANDIN H2 AND THROMBOXANE A2 ON SOME ISOLATED SMOOTH MUSCLE PREPARATIONS[J]. British Journal of Pharmacology, 1981, 73 3: 773-778. DOI:
10.1111/j.1476-5381.1981.tb16814.x[2] NOAH LIEL Perry V H Dale E Mais. Binding of a thromboxane A2/prostaglandin H2 agonist [3H]U46619 to washed human platelets[J]. Prostaglandins, 1987, 33 6: Pages 789-797. DOI:
10.1016/0090-6980(87)90107-9[3] PAULINA M. TYMKEWYCZ. Heterogeneity of thromboxane A2 (TP-) receptors: evidence from antagonist but not agonist potency measurements[J]. British Journal of Pharmacology, 1991, 102 3: 607-614. DOI:
10.1111/j.1476-5381.1991.tb12220.x[4] MARK ABRAMOVITZ . The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs[J]. Biochimica et biophysica acta. Molecular and cell biology of lipids, 2000, 1483 2: Pages 285-293. DOI:
10.1016/s1388-1981(99)00164-x
