Description
TPα and TPβ are two isoforms of the human TP receptor, the G protein-
coupled receptor (GPCR) that mediates the actions of thromboxane A
2 (TXA
2). Although their distinct physiological functions have not been fully elucidated, TPβ is believed to be responsible for vascular endothelial growth factor-
induced endothelial cell differentiation and migration whereas TPα appears to be the predominant isoform expressed in platelets. CAY10535 is a TP receptor antagonist that shows ~20-
fold selectivity for TPβ (IC
50 = 99 nM) relative to TPα (IC
50 = 1,970 nM) in the inhibition of U46619-
mediated Ca
2+ mobilization. This compound exhibits relatively poor activity on platelets (IC
50 = 985 nM) when inhibiting U-
46619-
induced platelet aggregation.
1
References
1. Hanson, J., Dogné, J.M., Ghiotto, J., et al.
Design, synthesis, and SAR study of a series of N-alkyl-N'-[2-(aryloxy)-5-nitrobenzenesulfonyl]ureas and -cyanoguanidine as selective antagonists of the TPα and TPβ isoforms of the human thromboxane A2 receptor J. Med. Chem. 50(16),3928-3936(2007).
