Zibotentan

Zibotentan (ZD4054) is a more selective and specific endothelin-A receptor (ETAR) antagonist with an IC50 value of 21 nM. Zibotentan inhibits endothelin-1 (ET-1) mediated processes associated with cancer progression, including invasion, metastasis, and angiogenesis. Zibotentan has no demonstrable effect on the endothelin-B receptor (ETBR), which promotes apoptosis (cell death). It is intended to be used in combination with docetaxel as an addition to standard chemotherapy for patients with metastatic CRPC. Zibotentan (ZD4054) has been shown to compete with 125I-ET-1 for binding to the cloned human ETA-receptor in vitro. Zibotentan treatment produced significant inhibition of tumor growth in ovarian and breast xenografts.