Table 4

 Peptide and non-peptide ET receptor antagonists*

ET receptor selectivity†
ETAETBETA/ETB
*The peptide compounds initially developed were subject to hydrolysation and subsequent inactivation, by peptidases in the gastrointestinal and circulatory system, and orally available, non-peptide antagonists are currently the main focus of clinical research.
†ETA selectivity is generally taken as >100-fold selectivity for the ETA over the ETB receptors and ETB selectivity as 10–100-fold selectivity for the ETB over the ETA receptors. Davenport AP. International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol Rev 2002;54:219–6.
Peptide antagonists
BQ123IRL2500TAK044
BQ485RES7011PD142893
BQ153BQ788PD145065
BQ610
FR139317
PD151242
Non-peptide antagonists in clinical development
Darusentan (approx 150-fold ETA selective v ETB)Enrasentan
Tezosentan (iv)
Ambrisentan (approx 260-fold ETA selective v ETB)
Atrasentan (approx 1860-fold ETA selective v ETB)Bosentan
Sitaxsentan (approx 6500-fold ETA selective v ETB)