GSK866   Click here for help

GtoPdb Ligand ID: 9653

PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GSK866 is a prototype of a class of compounds called selective glucocorticoid receptor agonists (SEGRAs). SEGRAs exert their pharmacological effect by activation of only the transrepression pathway, which is in contrast to traditional glucocorticosteroids which activate both the transactivation and transrepression pathways. Development of SEGRAs is aiming to improve the risk-benefit profile associated with use of traditional glucocorticosteroids drugs. See also our entry for mapracorat, a SEGRA that advanced to clinical trial. GSK866 is example 1 in [1], which is shown bound to the glucocortocoid receptor in the X-ray structure 3E7C. A series of novel covalently binding SEGRAs based on the structure of GSK866 is reported in [2]. Note that there is some ambiguity in the literature and online chemistry resources as to the precise stereochemistry of this ligand. We show the S isomer as specificed by the SMILES string supplied in the PDB entry.
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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 7
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 112.96
Molecular weight 561.1
XLogP 5.52
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 CCN(C(=O)c1c(Cl)cccc1Cl)CC(C(F)(F)F)(CNC(=O)c1cnn(c1N)c1ccc(cc1)F)O
Isomeric SMILES CCN(C(=O)c1c(Cl)cccc1Cl)C[C@](C(F)(F)F)(CNC(=O)c1cnn(c1N)c1ccc(cc1)F)O
InChI InChI=1S/C23H21Cl2F4N5O3/c1-2-33(21(36)18-16(24)4-3-5-17(18)25)12-22(37,23(27,28)29)11-31-20(35)15-10-32-34(19(15)30)14-8-6-13(26)7-9-14/h3-10,37H,2,11-12,30H2,1H3,(H,31,35)/t22-/m0/s1
InChI Key LKQMULLPLYLIGW-QFIPXVFZSA-N
References
1. Madauss KP, Bledsoe RK, Mclay I, Stewart EL, Uings IJ, Weingarten G, Williams SP. (2008)
The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist.
Bioorg Med Chem Lett, 18 (23): 6097-9. [PMID:18952422]
2. Ryabtsova O, Joossens J, Van Der Veken P, Vanden Berghe W, Augustyns K, De Winter H. (2016)
Novel selective glucocorticoid receptor agonists (SEGRAs) with a covalent warhead for long-lasting inhibition.
Bioorg Med Chem Lett, 26 (20): 5032-5038. [PMID:27612544]