Zibotentan(ZD4054) is an orally administered, potent and specific ETA-receptor (endothelin A receptor) antagonist (IC50 = 21 nM). It was first evaluated as a potential treatment for pulmonary arterial hypertension in the late 1990s. Subsequently, interest switched to the role of endothelins in cancer, particularly hormone-resistant prostate cancer (HRPC). In vitro, Zibotentan(ZD4054) has been shown to compete with 125I-ET-1 for binding to the cloned human ETA-receptor with an IC50 value of 21 nM. No binding to the ETB receptor was observed with concentrations of zibotentan in excess of 10 ¦ÌM. This agent is capable of inhibiting or reducing the multitude of effects that are evoked by ET-1 activation of the ETA receptor and which promote tumor survival, growth and progression. Zibotentan(ZD4054) treatment produced significant inhibition of tumor growth in ovarian and breast xenografts.