GSK-J1   Click here for help

GtoPdb Ligand ID: 7027

PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GSK-J1 is a catalytic site inhibitor that is somewhat selective for the H3K27me3-specific demethylases KDM6A and 6B (a.k.a. UTX and JMJD3 respectively) [2]. The compund has also been shown to inhibit H3K4me3/me2 catalysed by KDM5 enzymes in vitro [1].
This is a compound from the Structural Genomics Consortium's (SGC) Epigenetics Probes Collection. It reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX.
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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

GSK-J1 is commercially available from our sponsors

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 2
Rotatable bonds 6
Topological polar surface area 91.24
Molecular weight 389.19
XLogP 3.71
No. Lipinski's rules broken 0
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 OC(=O)CCNc1nc(nc(c1)N1CCc2ccccc2CC1)c1ccccn1
Isomeric SMILES OC(=O)CCNc1nc(nc(c1)N1CCc2ccccc2CC1)c1ccccn1
InChI InChI=1S/C22H23N5O2/c28-21(29)8-12-24-19-15-20(26-22(25-19)18-7-3-4-11-23-18)27-13-9-16-5-1-2-6-17(16)10-14-27/h1-7,11,15H,8-10,12-14H2,(H,28,29)(H,24,25,26)
InChI Key AVZCPICCWKMZDT-UHFFFAOYSA-N
References
1. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M, Gerlach LO, Birk P, Helin K. (2014)
Inhibition of demethylases by GSK-J1/J4.
Nature, 514 (7520): E1-2. [PMID:25279926]
2. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H et al.. (2012)
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response.
Nature, 488 (7411): 404-8. [PMID:22842901]
3. Mackeen MM, Kramer HB, Chang KH, Coleman ML, Hopkinson RJ, Schofield CJ, Kessler BM. (2010)
Small-molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry.
J Proteome Res, 9 (8): 4082-92. [PMID:20583823]
4. Sakurai M, Rose NR, Schultz L, Quinn AM, Jadhav A, Ng SS, Oppermann U, Schofield CJ, Simeonov A. (2010)
A miniaturized screen for inhibitors of Jumonji histone demethylases.
Mol Biosyst, 6 (2): 357-64. [PMID:20094655]