streptonigrin   Click here for help

GtoPdb Ligand ID: 8683

Synonyms: bruneomycin | nigrin | NSC-45383 | rufocromomycin | valacidin
Compound class: Natural product
Comment: Streptonigrin is an antibacterial with anti-tumour effects ascribed to its substituted quinolinequinoic fragment [3]. Streptonigrin is isolated from Streptomyces flocculus or S. rufochronmogenus. This compound is reported to be a selective inhibitor of protein-arginine deiminase type-IV (PADI4) [1].
The ChEMBL entry for streptonigrin (CHEMBL11417) represents an alternative tautomer to the structure shown here.
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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

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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 11
Hydrogen bond donors 4
Rotatable bonds 5
Topological polar surface area 196.92
Molecular weight 506.14
XLogP -0.51
No. Lipinski's rules broken 1

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 COC1=C(OC)C=CC(=c2c(N)c([nH]c(c2C)C(=O)O)c2ccc3c(n2)C(=O)C(=C(C3=O)OC)N)C1=O
Isomeric SMILES COC1=C(OC)C=C/C(=c\2/c(N)c([nH]c(c2C)C(=O)O)c2ccc3c(n2)C(=O)C(=C(C3=O)OC)N)/C1=O
InChI InChI=1S/C25H22N4O8/c1-9-14(10-6-8-13(35-2)23(36-3)20(10)30)15(26)19(29-17(9)25(33)34)12-7-5-11-18(28-12)22(32)16(27)24(37-4)21(11)31/h5-8,29H,26-27H2,1-4H3,(H,33,34)/b14-10-
InChI Key DLWOTOMWYCRPLK-UVTDQMKNSA-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
Although IC50 values appear to show preference for PADI3 inhibition, experiments show that streptonigrin is an irreversible inhibitor which covalently modifies the active site of the enzyme. In addition, as the substrate used in the experiments is a poor substrate for PADI3, this has skewed the results. Additional experiments to calculate the kinact/KI values (a more appropriate measure of irreversible inhibition) point to selectivity for PADI4 [2]. The kinact/KI value for PADI4 is 4.4x105 M-1 min-1 and for PADI3 it is 3.5x103 M-1 min-1 (indicating >120-fold selectivity).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
peptidyl arginine deiminase 3 N/A Inhibitor Inhibition 6.4 pIC50 -
⤷ pIC50 6.4 (IC50 4.3x10-7 M)
peptidyl arginine deiminase 4 Primary target of this compound N/A Inhibitor Inhibition 5.6 pIC50 - 2
⤷ pIC50 5.6 (IC50 2.5x10-6 M) [2]