Zibotentan

SKU: orb1687464

Description

Zibotentan (ZD4054) is a potent and selective endothelin A (ETA) receptor antagonist with an IC50 of 21 nM, showing no affinity for the ETB receptor. This investigational compound has been evaluated in Phase 3 clinical trials, primarily for oncology research such as prostate cancer, and is used in vitro and in vivo to study endothelin-mediated pathways.

Research Area

Cell Biology, Pharmacology & Drug Discovery

Images & Validation

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Key Properties

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CAS Number	186497-07-4
MW	424.43
Purity	99.57% (May vary between batches)
Formula	C₁₉H₁₆N₆O₄S
SMILES	COc1nc(C)cnc1NS(=O)(=O)c1cccnc1-c1ccc(cc1)-c1nnco1
Target	Apoptosis,Endothelin Receptor
Solubility	DMSO:23 mg/mL (54.19 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+90% Corn Oil:2 mg/mL (4.71 mM)

Bioactivity

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Target IC50	ETA:21 nM
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. Read more...
In Vitro	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. Read more...
Cell Research	Cells are serum starved by incubation for 24 hours in serum-free DMEM before exposed to Zibotentan for 48 hours. After the treatment, cells are lysed and the supernatant is recovered and assayed for histone-associated DNA fragments, at 405 nm by the use of a microplate reader. For detection of early apoptotic events, floating and adherent cells are collected. Cells are double stained with FITC-conjugated Annexin V and propidium iodide using the Vybrant Apoptosis Kit and are immediately analyzed by cytofluorometric analysis.(Only for Reference) Read more...

Storage & Handling

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Storage	Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

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Inhibitor, ET-A, ETA, EndothelinReceptor, Endothelin Receptor, inhibit, Apoptosis, anticancer, bcl-2, 44MAPK, caspase-3, CRPC, ZD4054, ZD-4054, ZD 4054, Zibotentan, p42

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Compound Identifiers

PubChem CID

9910224 ↗

Key Properties

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No computed properties available.

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Zibotentan

Description

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Key Properties

Bioactivity

Storage & Handling

Alternative Names

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Compound Identifiers

Key Properties

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Zibotentan (orb1687464)

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