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Zibotentan

Cat. No. M1816

Zibotentan Structure

Synonym: ZD4054

Size Price Availability Quantity
5mg USD 145 In stock
10mg USD 265 In stock
50mg USD 820 In stock
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Quality Control
Biological Activity

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.

Protocol
Cell Experiment
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.
Concentrations 1 μmol/L
Incubation time 24 h
Animal Experiment
Animal models HEY cells Xenografts in nude mice
Formulation diluted in PBS
Dosages 10 mg/kg/d for 21 days
Administration i.p.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
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.

Chemical Information
Molecular Weight 424.43
Formula C19H16N6O4S
CAS Number 186497-07-4
Purity >99%
Solubility DMSO ≥14 mg/mL
Storage at -20°C
References

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.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Zibotentan, ZD4054 supplier, Endothelin Receptor, inhibitors

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