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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2D Structure
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Physico-chemical Properties
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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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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
References
1. Cleasby A, Yon J, Day PJ, Richardson C, Tickle IJ, Williams PA, Callahan JF, Carr R, Concha N, Kerns JK et al.. (2014)
Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO.
PLoS ONE, 9 (6): e98896. [PMID:24896564]
2. Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW et al.. (2005)
Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress.
Proc. Natl. Acad. Sci. U.S.A., 102 (12): 4584-9. [PMID:15767573]
3. Rojas-Rivera J, Ortiz A, Egido J. (2012)
Antioxidants in kidney diseases: the impact of bardoxolone methyl.
Int J Nephrol, 2012: 321714. [PMID:22701794]
4. Wang Y, Porter WW, Suh N, Honda T, Gribble GW, Leesnitzer LM, Plunket KD, Mangelsdorf DJ, Blanchard SG, Willson TM, Sporn MB. (2000)
A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma.
Mol. Endocrinol., 14 (10): 1550-6. [PMID:11043571]
5. Wu J, Liu X, Fan J, Chen W, Wang J, Zeng Y, Feng X, Yu X, Yang X. (2014)
Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.
Toxicology, 318: 22-31. [PMID:24530882]