Zibotentan (ZD4054)

Zibotentan (ZD4054; CAS 186497-07-4) is a selective antagonist of the endothelin A receptor (ET_AR). The endothelin-1 (ET-1)/ET_AR signaling axis is implicated in ovarian cancer progression. In vitro studies in ET_AR-positive human ovarian cancer cell lines demonstrate that Zibotentan decreases basal and ET-1-stimulated proliferation, suppresses phosphorylation of AKT and p42/44 MAPK, reduces anti-apoptotic protein bcl-2 expression, and elevates active caspase-3 levels, enhancing apoptosis. In vivo, Zibotentan inhibits tumor growth in HEY ovarian carcinoma xenograft models, reducing proliferation index, microvascular density, and MMP-2 expression, and augments paclitaxel's antitumor activity. Clinically, pharmacokinetic assessments in advanced solid tumor patients indicate consistent safety profiles across patient populations.