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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Zibotentan (formerly known as ZD-4054; ZD4054) is a specific and orally bioavailable Endothelin (ET)A antagonist with potential antitumor activity. It shows no action against ETB and has an IC50 of 21 nM for inhibiting the endothelin receptor. The FDA approved zibotentan for prostate cancer treatment on a fast track basis; however, the drug did not pass clinical trials. By selectively binding to the ET-A receptor, zibotentan blocks the actions of endothelin that stimulate the growth of tumor cells. By blocking AKT and p42/44MAPK phosphorylation, ZD4054 successfully reduced basal and ET-1-induced cell proliferation. It also enhanced apoptosis by blocking Bcl-2, activating caspase-3, and poly(ADP-ribose) polymerase protein.
| Targets |
ET-A ( IC50 = 21 nM )
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| ln Vivo |
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| Enzyme Assay |
The inhibition by Zibotentan (varying concentrations) of 125iodine-ET-1 binding to cloned human ETA is assessed using standard radioligand-binding techniques. Mice erythroleukaemic cells are used to express human recombinant ETA, and cell membranes are prepared for competitive binding experiments using 125iodine-ET-1 as the radioligand. In vitro experiments with Zibotentan are conducted in triplicate, ranging from 100 pM to 100 μM in half-log increments. The expression used to quantify the inhibition of ET-1 binding is the geometric mean pIC50 value, which represents the concentration required to inhibit 50% of binding, along with a 95% confidence interval (CI). Zibotentan's affinity for cloned human ETA is evaluated by applying Cheng and Prusoff's equation to find the equilibrium dissociation constant (Ki) in an additional receptor-binding screen that makes use of more concentration-response curves from three different studies.
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| Cell Assay |
After a 24-hour incubation period in serum-free DMEM, cells are subjected to a 48-hour Zibotentan exposure. Following therapy, cells are lysed, the supernatant is extracted, and using a microplate reader, the assay is performed to look for histone-associated DNA fragments at 405 nm. Adherent and floating cells are collected for the purpose of detecting early apoptotic events. Using the Vybrant Apoptosis Kit, cells are double stained with propidium iodide and FITC-conjugated Annexin V. Their cytofluorometric analysis is then performed right away.
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| Animal Protocol |
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| References | |||
| Additional Infomation |
N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide is a phenylpyridine.
Zibotentan is an orally available selective antagonist of the endothelin-A (ET-A) receptor with potential antineoplastic activity. Zibotentan binds selectively to the ET-A receptor, thereby inhibiting endothelin-mediated mechanisms that promote tumor cell proliferation. Drug Indication Investigated for use/treatment in prostate cancer. |
| Molecular Formula |
C19H16N6O4S
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| Molecular Weight |
424.43
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| Exact Mass |
424.095
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| Elemental Analysis |
C, 53.77; H, 3.80; N, 19.80; O, 15.08; S, 7.55
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| CAS # |
186497-07-4
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| Related CAS # |
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| PubChem CID |
9910224
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
637.0±65.0 °C at 760 mmHg
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| Flash Point |
339.0±34.3 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.628
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| LogP |
2.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
654
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(NC1=NC=C(C)N=C1OC)(C2=CC=CN=C2C3=CC=C(C4=NN=CO4)C=C3)=O
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| InChi Key |
FJHHZXWJVIEFGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16N6O4S/c1-12-10-21-17(19(23-12)28-2)25-30(26,27)15-4-3-9-20-16(15)13-5-7-14(8-6-13)18-24-22-11-29-18/h3-11H,1-2H3,(H,21,25)
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| Chemical Name |
N-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3561 mL | 11.7805 mL | 23.5610 mL | |
| 5 mM | 0.4712 mL | 2.3561 mL | 4.7122 mL | |
| 10 mM | 0.2356 mL | 1.1781 mL | 2.3561 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A Study to Assess Zibotentan Pharmacokinetics in Participants With Moderate Hepatic and Moderate Renal Impairment
CTID: NCT05112419
Phase: Phase 1 Status: Completed
Date: 2022-01-27
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