bardoxolone   Click here for help

GtoPdb Ligand ID: 2717

Synonyms: CDDO | RTA-401
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Bardoxolone was a Phase 3 NF-κB signaling inhibitor [2]. Although the recommended INN for this compound is bardoxolone, it is administered as bardoxolone methyl which has ChEMBL ID CHEMBL1762621. Bardoxolone can be described as a KEAP1 antagonist, as it antigonises KEAP1 interaction with the Nrf2 transription factor [1]. As this action releases Nrf2 from the inhibitory effect of the protein-protein interaction, it can also be described as a functional Nrf2 activator.
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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.

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View interactive charts of activity data across species
2D Structure
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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.

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Physico-chemical Properties
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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.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 95.23
Molecular weight 491.3
XLogP 6.3
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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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.

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Canonical SMILES N#CC1=CC2(C)C(C(C1=O)(C)C)CCC1(C2=CC(=O)C2C1(C)CCC1(C2CC(C)(C)CC1)C(=O)O)C
Isomeric SMILES N#CC1=C[C@@]2(C)[C@H](C(C1=O)(C)C)CC[C@@]1(C2=CC(=O)[C@H]2[C@@]1(C)CC[C@@]1([C@H]2CC(C)(C)CC1)C(=O)O)C
InChI InChI=1S/C31H41NO4/c1-26(2)10-12-31(25(35)36)13-11-30(7)23(19(31)16-26)20(33)14-22-28(5)15-18(17-32)24(34)27(3,4)21(28)8-9-29(22,30)6/h14-15,19,21,23H,8-13,16H2,1-7H3,(H,35,36)/t19-,21-,23-,28-,29+,30+,31-/m0/s1
InChI Key TXGZJQLMVSIZEI-UQMAOPSPSA-N
No information available.
Summary of Clinical Use Click here for help
Clinical trials for treatment of chronic kidney disease (CKD) as a result of type 2 diabetes mellitus have been terminated. Visit ClinicalTrials.gov to view currently registered drug trials involving this compound.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Bardoxolone inhibits the ubiquitinisation activity of KEAP1, a protein which interacts with and ubiquitinises the Nrf2 transcription factor (NFE2L2, Q16236) and sequesters Nrf2 to the cytoplasm. Bardoxolone-induced activation of Nrf2 leads to activation of Keap1-Nrf2 pathway which regulates genes (containing antioxidant response elements (AREs)) involved in antioxidant and anti-inflammatory responses [2-3,5].