CAY10535 Exclusive

Description

TPα and TPβ are two isoforms of the human TP receptor, the G protein-coupled receptor (GPCR) that mediates the actions of thromboxane A₂ (TXA₂). 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 (IC₅₀ = 99 nM) relative to TPα (IC₅₀ = 1,970 nM) in the inhibition of U46619-mediated Ca²⁺ mobilization. This compound exhibits relatively poor activity on platelets (IC₅₀ = 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).