marbostat-100   Click here for help

GtoPdb Ligand ID: 9891

Synonyms: compound 5a [PMID: 29589441]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Marbostat-100 is a histone deacetylase (HDAC) inhibitor that is selective for HDAC6 [3]. It is a lead structure identified by structure-activity-relationship and medicinal chemistry efforts. HDAC6 isoform-specific compounds are predicted to provide anti-inflammatory activity relevant to the treatment of chronic immune and inflammatory disorders.
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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 2
Rotatable bonds 4
Topological polar surface area 94.88
Molecular weight 404.15
XLogP 1.68
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES ONC(=O)c1ccc(cc1)Cn1c2CN3CC(c2c2c1cccc2)C(=O)N(C3=O)C
Isomeric SMILES ONC(=O)c1ccc(cc1)Cn1c2CN3CC(c2c2c1cccc2)C(=O)N(C3=O)C
InChI InChI=1S/C22H20N4O4/c1-24-21(28)16-11-25(22(24)29)12-18-19(16)15-4-2-3-5-17(15)26(18)10-13-6-8-14(9-7-13)20(27)23-30/h2-9,16,30H,10-12H2,1H3,(H,23,27)
InChI Key ZCAIUGLOTHAUQX-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
Marbostat-100 is more selective than previously identified HDAC6 inhibitors [1-2,4], and its potency is retained in vitro and in vivo, such that its biological effects are not confounded by off-target activity at higher doses. There is very little difference in the potency of the (S) and (R) enantiomers of marbostat-100 vs. HDAC6 (S-marbostat-100 Ki 0.7 nM, R-marbostat-100 Ki 2.01 nM) [3].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
histone deacetylase 6 Primary target of this compound Hs Inhibitor Inhibition 9.1 pKi - 3
⤷ pKi 9.1 (Ki 7x10-10 M) [3]
Description: In vitro biochemical assay using recombinant purified human HDAC6.
histone deacetylase 8 Hs Inhibitor Inhibition 6.8 pKi - 3
⤷ pKi 6.8 (Ki 1.73x10-7 M) [3]
Description: In vitro biochemical assay using recombinant purified human HDAC8.
histone deacetylase 2 Hs Inhibitor Inhibition 6.1 pKi - 3
⤷ pKi 6.1 (Ki 7.74x10-7 M) [3]
Description: In vitro biochemical assay using recombinant purified human HDAC2.