Molecular Weight(MW): 424.43
Zibotentan (ZD4054) is a specific Endothelin (ET)A antagonist with IC50 of 21 nM, exhibiting no activity at ETB. Phase 3.
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(E and F) Photomicrograph and quantifications showing reducing in inflammation in steatosis in IL27RA-/-p53H/1 mice treated with ZD4054 (N=9), when compared to sham treated mice (N=7). Chi-square test was used to determine the differences among these two groups. In vivo data with ZD4054 inhibitor was repeated twice with similar results. (i) WT, (ii) IL27RA-/-, (iii) p53H/1, or (iv) IL27RA-/-p53H/1. Dots indicate data from liver of individual mice. Pictures taken at 2003. *P < 0.05. Abbreviation: DAPI, 40,6-diamidino-2-phenylindole.
Hepatology, 2016, 63(3):1000-12. . Zibotentan (ZD4054) purchased from Selleck.
Purity & Quality Control
Choose Selective Endothelin Receptor Inhibitors
|Description||Zibotentan (ZD4054) is a specific Endothelin (ET)A antagonist with IC50 of 21 nM, exhibiting no activity at ETB. Phase 3.|
As Zibotentan specifically inhibits ETA-mediated antiapoptotic effects, but not ETB-mediated proapoptotic effects in human and rat smooth muscle cells, Zibotentan binds to endothelin A receptor (ETA) with high affinity with Ki of 13 nM, and has no affinity for endothelin B receptor (ETB) with IC50 of >10 μM.  Zibotentan treatment at 1 μM inhibits ET-1 induced mitogenic activity in ovarian carcinoma cell lines HEY and OVCA 433 secreting ET-1 and expressing ETA and ETB mRNA.  ZD4054 (1 μM) inhibits ET-1 induced EGFR transactivation in HEY and OVCA 433 cells. Zibotentan (1 μM) reverts ET-1 mediated epithelial-mesenchymal transition (EMT), by enhancing E-cadherin expression and promoter activity, and inhibiting vascular endothelial growth factor (VEGF) secretion and invasiveness in HEY and OVCA 433 cells.  Zibotentan also potently inhibits the basal and ET-1 induced cell proliferation in SKOV-3 and A-2780 cells, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins. 
|In vivo||Administration of Zibotentan at 10 mg/kg/day for 21 days potently inhibits the growth of HEY ovarian carcinoma xenografts in mice by 69% with no associated toxicity, which is in association with the blocking of cell proliferation evaluated by 37% inhibition of the Ki-67 expression, and the 62% inhibition of tumor-induced vascularization. Consistently, Zibotentan treatment significantly inhibits the expression of matrix metalloproteinase-2 (MMP-2) and VEGF, as well as the activation of p42/44 MAPK and EGFR, and potently enhances the expression of E-cadherin. |
Receptor-binding assays:The inhibition by Zibotentan (varying concentrations) of 125iodine-ET-1 binding to cloned human ETA is assessed using standard radioligand-binding techniques. Human recombinant ETA is expressed in mouse erythroleukaemic cells, and cell membranes prepared for competitive binding studies using 125iodine-ET-1 as the radioligand. Incubations are carried out in triplicate in the presence of Zibotentan, 100 pM to 100 μM in half-log increments, and inhibition of ET-1 binding is expressed as the geometric mean pIC50 value (concentration to inhibit 50% of binding) with a 95% confidence interval (CI). The affinity of Zibotentan for cloned human ETA is also assessed using the equation of Cheng and Prusoff to determine the equilibrium dissociation constant (Ki) in a further receptor-binding screen utilizing a greater number of concentration-response curves determined in three separate studies.
|In vitro||DMSO||24 mg/mL (56.54 mM)|
|Water||slightly soluble or insoluble|
|Ethanol||slightly soluble or insoluble|
|In vivo||1% DMSO+30% polyethylene glycol+1% Tween 80||30 mg/mL|
* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
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Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02047708||Recruiting||Scleroderma|Scleroderma Renal Crisis|Chronic Kidney Disease||University College, London|Medical Research Council||October 2014||Phase 2|
|NCT01890135||Completed||Peripheral Arterial Disease|Intermittent Claudication||University of Virginia|National Institutes of Health (NIH)||June 2013||Phase 2|
|NCT01134497||Unknown status||Metastatic Breast Cancer||Cardiff University||September 2010||Phase 2|
|NCT01119118||Terminated||Prostate Cancer||University of Wisconsin, Madison|AstraZeneca||April 2010||Phase 2|
|NCT01205711||Completed||Colorectal Cancer||Cardiff University||April 2010||Phase 2|
|NCT00997945||Completed||Advanced Solid Malignancies||AstraZeneca||October 2009||Phase 1|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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