zibotentan   Click here for help

GtoPdb Ligand ID: 3539

Synonyms: ZD 4054 | ZD-4054 | ZD4054
Compound class: Synthetic organic
Comment: Zibotentan is an endothelin receptor antagonist.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 141.37
Molecular weight 424.1
XLogP 3.54
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES COc1nc(C)cnc1NS(=O)(=O)c1cccnc1c1ccc(cc1)c1nnco1
Isomeric SMILES COc1nc(C)cnc1NS(=O)(=O)c1cccnc1c1ccc(cc1)c1nnco1
InChI 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)
InChI Key FJHHZXWJVIEFGJ-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Zibotentan was assessed as an anti-cancer treatment, but development was discontinued due to lack of efficacy. It has more recently been repurposed, with trials progressing for chronic kidney disease (CKD), in which the combination of zibotentan and dapagliflozin is being evaluated. The diuretic effects of dapagliflozin are predicted to counter-act the fluid retention associated with zibotentan-mediated endothelin A receptor antagonism [3] and to enhance the therapeutic benefit of the drug combination compared to dapagliflozin monotherapy in CKD patients.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT06087835 Study to Investigate Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin in Participants With Chronic Kidney Disease and High Proteinuria (ZENITH High Proteinuria) Phase 3 Interventional AstraZeneca
NCT05570305 Zibotentan and Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria Phase 2 Interventional University Medical Center Groningen
NCT04724837 Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial) Phase 2 Interventional AstraZeneca 1