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.
|Cell lines||OVCA 433 and HEY cells|
|Preparation method||Cell proliferation assay.
[3H]thymidine incorporation was measured as previously described ( 5). Cells were seeded in 96-well plates at ∼80% confluence (2 × 106 per well) and incubated in serum-free medium for 24 h to induce quiescence and 100 nmol/L ET-1 was added. Responses to all treatments were assayed in sextuplicate, and results were expressed as the means of three separate experiments.
|Incubation time||24 h|
|Animal models||HEY cells Xenografts in nude mice|
|Formulation||diluted in PBS|
|Dosages||10 mg/kg/d for 21 days|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO ≥14 mg/mL|
Pharmacokinetics and tolerability of zibotentan (ZD4054) in subjects with hepatic or renal impairment: two open-label comparative studies.
Tomkinson H, et al. BMC Clin Pharmacol. 2011 Mar 17;11:3. PMID: 21414193.
Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.
Trump DL, et al. Prostate. 2011 Sep;71(12):1264-75. PMID: 21271613.
Zibotentan for the treatment of castrate-resistant prostate cancer.
Shepard DR, et al. Expert Opin Investig Drugs. 2010 Jul;19(7):899-908. PMID: 20497097.
Combined targeting of endothelin A receptor and epidermal growth factor receptor in ovarian cancer shows enhanced antitumor activity.
Rosanò L, et al. Cancer Res. 2007 Jul 1;67(13):6351-9. PMID: 17616694.
|Related Endothelin Receptor Products|
Ro 46-2005 is a novel synthetic non-peptide endothelin receptor antagonist, inhibits the specific binding of 125I-ET-1 to human vascular smooth muscle cells (ETA receptor) with IC50 of 220 nM.
Bosentan is an endothelin (ET) receptor antagonist for ET-A and ET-B with Ki of 4.7 nM and 95 nM, respectively.
Bosentan is an endothelin (ET) receptors antagonist for ET-A and ET-B with Ki of 4.7 nM and 95 nM, respectively.
Macitentan is an orally-active, tissue-targeting dual ET receptor antagonist.
Sitaxsentan (TBC-11251) is an orally active, highly selective antagonist of endothelin A receptors.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.