In vitro characterisation of Ro 46‐8443, the first non‐peptide antagonist selective for the endothelin ETB receptor

Abstract
We describe here Ro 46-8443, the first non-peptide endothelin ETB receptor selective antagonist. It displays up to 2000-fold selectivity for ETB receptors both in terms of binding inhibitory potency and functional inhibition. The observed parallel rightward shift of concentration-response curves with different antagonist concentrations is consistent with a competitive binding mode. Since Ro 46-8443 selectively inhibits ETB receptor mediated responses, it is a valuable tool for clarifying the role of ETB receptors in pathology.