CPUY192018   Click here for help

GtoPdb Ligand ID: 9710

Synonyms: compound 18e [PMID: 26258437] | compound 2 [PMID: 24512214]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: CPUY192018 binds to kelch like ECH associated protein 1 (KEAP1) and prevents its interaction with the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2; NFE2L2; Q16236) [2-3]. CPUY192018 acts as a functional Nrf2 activator. It binds non-covalently to KEAP1, unlike the approved Nrf2 activator dimethyl fumarate and the failed clinical lead bardoxolone, which form irreversible, covalent bonds with a key cysteine residue in KEAP1 [1].
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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 10
Hydrogen bond donors 2
Rotatable bonds 12
Topological polar surface area 184.58
Molecular weight 614.1
XLogP 4.39
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 COc1ccc(cc1)S(=O)(=O)N(c1ccc(c2c1cccc2)N(S(=O)(=O)c1ccc(cc1)OC)CC(=O)O)CC(=O)O
Isomeric SMILES COc1ccc(cc1)S(=O)(=O)N(c1ccc(c2c1cccc2)N(S(=O)(=O)c1ccc(cc1)OC)CC(=O)O)CC(=O)O
InChI InChI=1S/C28H26N2O10S2/c1-39-19-7-11-21(12-8-19)41(35,36)29(17-27(31)32)25-15-16-26(24-6-4-3-5-23(24)25)30(18-28(33)34)42(37,38)22-13-9-20(40-2)10-14-22/h3-16H,17-18H2,1-2H3,(H,31,32)(H,33,34)
InChI Key KWSIQJUNYMMCTB-UHFFFAOYSA-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. Jiang ZY, Lu MC, Xu LL, Yang TT, Xi MY, Xu XL, Guo XK, Zhang XJ, You QD, Sun HP. (2014)
Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis.
J Med Chem, 57 (6): 2736-45. [PMID:24512214]
3. Jiang ZY, Xu LL, Lu MC, Chen ZY, Yuan ZW, Xu XL, Guo XK, Zhang XJ, Sun HP, You QD. (2015)
Structure-Activity and Structure-Property Relationship and Exploratory in Vivo Evaluation of the Nanomolar Keap1-Nrf2 Protein-Protein Interaction Inhibitor.
J Med Chem, 58 (16): 6410-21. [PMID:26258437]
4. Lu MC, Ji JA, Jiang YL, Chen ZY, Yuan ZW, You QD, Jiang ZY. (2016)
An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis.
Sci Rep, 6: 26585. [PMID:27215610]