ETA receptor antagonist,potent and specific
CAS：186497-07-4
分子式：C19H16N6O4S
分子量：424.43
纯度：98%
存储：Store at -20°C

Background:

ZD4054 is a specific antagonist of the endothelin A receptor.

The autocrine endothelin (ET)-1/endothelin A receptor (ETAR) pathway is an important regulator of several processes involved in ovarian cancer progression.

In vitro: In the human ovarian cancer ETAR positive cell lines, ZD4054 effectively inhibited the basal and ET-1-induced cell proliferation, with the inhibition of AKT and p42/44MAPK phosphorylation, and increased apoptosis, through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins. [1].

In vivo: In HEY ovarian cancer xenografts, ZD4054 inhibited tumor growth to the same degree as paclitaxel. Moreover, ZD4054-dependent tumor growth inhibition was associated with a reduction in proliferation index, MMP-2 expression, and microvessel microvessel density [2].

Clinical trial: The PK and safety profiles of ZD4054 determined in this Chinese patient population are similar to those previously reported. Findings suggest no clinically relevant inter-ethnic differences in ZD4054 disposition between the patient populations analyzed [3].

参考文献:
[1] Morris CD, Rose A, Curwen J, Hughes AM, Wilson DJ, Webb DJ.  Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence. Br J Cancer. 2005 Jun 20;92(12):2148-52.
[2] Rosanò L, Di Castro V, Spinella F, Nicotra MR, Natali PG, Bagnato A.  ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo. Mol Cancer Ther. 2007 Jul;6(7):2003-11.
[3] Li J, Liu Y, Qian J, Wu L, Kemp J, Nii M, Tomkinson H, Zuo Y, Ranson M, Usami M.  Single- and multiple-dose pharmacokinetics, safety and tolerability of zibotentan (ZD4054) in Chinese men with advanced solid tumors. Cancer Chemother Pharmacol. 2012 Jul;70(1):57-63.