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EBL-3599   Click here for help

GtoPdb Ligand ID: 14229

Compound class: Synthetic organic
Comment: EBL-3599 is from a series of antibacterial compounds that target UDP-2,3-diacylglucosamine hydrolase (LpxH), an essential enzyme in the lipopolysaccharide synthesis pathway, that is conserved in the majority of Gram-negative bacteria but absent in human [1]. EBL-3599 is a derivative of JEDI-1444 and was identified as part of a programme to develop LpxH inhibitors with activity against efflux-proficient Gram-negative bacteria.
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 14
Hydrogen bond donors 3
Rotatable bonds 13
Topological polar surface area 210.42
Molecular weight 655.79
XLogP -1.27
No. Lipinski's rules broken 3

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 CC1=NC(=NC(=C1)C#N)N2CCN(CC2)S(=O)(=O)C3=CC=C(C=C3)NC(=O)C4=CC(=CC=C4N(C)S(=O)(=O)C)CNCCCN
Isomeric SMILES CC1=CC(=NC(=N1)N2CCN(CC2)S(=O)(=O)C3=CC=C(C=C3)NC(=O)C4=C(C=CC(=C4)CNCCCN)N(C)S(=O)(=O)C)C#N
InChI InChI=1S/C29H37N9O5S2/c1-21-17-24(19-31)35-29(33-21)37-13-15-38(16-14-37)45(42,43)25-8-6-23(7-9-25)34-28(39)26-18-22(20-32-12-4-11-30)5-10-27(26)36(2)44(3,40)41/h5-10,17-18,32H,4,11-16,20,30H2,1-3H3,(H,34,39)
InChI Key JHQIDWIWOVDFPG-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
EBL-3599 exhibits Gram-negative antibacterial activity and is effective against efflux-proficient strains of Escherichia coli and Klebsiella pneumoniae [1]. It has improved drug-like properties, compared to earlier inhibitors from the series, and shown to have in vivo efficacy against E. coli and K. pneumoniae in a mouse peritonitis model [1].
EBL-3599 inhibits E.coli LpxH with an IC50 of 3.5 nM [1].