Zibotentan (ZD4054) - 10mM in DMSO, high purity , CAS No.186497-07-4(DMSO)

Item Number
Z408265
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Z408265-1ml
1ml
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Endothelin Receptor Antagonists

Basic Description

Specifications & PurityMoligand™, 10mM in DMSO
Biochemical and Physiological MechanismsZibotentan (ZD4054) is a specific Endothelin (ET)A antagonist with IC50 of 21 nM, exhibiting no activity at ETB. Phase 3.
Storage TempStore at -80°C
Shipped InIce chest + Ice pads
GradeMoligand™
Product Description

Information

Zibotentan (ZD4054) Zibotentan (ZD4054) is a specific Endothelin (ET)A antagonist with IC50 of 21 nM, exhibiting no activity at ETB. Phase 3.
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.

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.
Cell Data

cell lines:U87, MT330, SJ-G2, and GBM6 human glioma lines

Concentrations:Dissolved in DMSO, final concentrations 1 μM

Incubation Time:48 hours

Powder Purity:≥99%

Associated Targets(Human)

EDNRA Tclin Endothelin-1 receptor (2 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)

Names and Identifiers

Canonical SMILES COC1=NC(=CN=C1N[S](=O)(=O)C2=CC=CN=C2C3=CC=C(C=C3)C4=NN=CO4)C
Molecular Weight 424.43

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