JBI-589   Click here for help

GtoPdb Ligand ID: 12481

Synonyms: compound 13 [WO2022034616A1] | JBI589
PDB Ligand
Compound class: Synthetic organic
Comment: JBI-589 is an orally bioavailable, pharmacological inhibitor of peptidyl arginine deiminase 4 (PADI4) [2-3]. PADI4 is involved in several biological processes, including neutrophil extracellular trap (NET) formation that is an important component of the innate immune system and defence against invading pathogens. Elevated PADI4 activity can induce dysregulated NETosis that triggers a cascade of inflammatory reactions that can promote autoimmune diseases, cancer cell metastasis, and damage to surrounding tissues. PADI4 inhibitors are being considered for conditons that are associated with NETosis.
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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

JBI-589 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 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 6
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 65.17
Molecular weight 481.57
XLogP 2.7
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 CC1=C(C2=CC3=C(C=CC=C3)N2CC4=CC=C(C=C4)F)N=C5C=C(C=CN15)C(=O)N6CCC[C@H](C6)N
Isomeric SMILES CC1=C(N=C2C=C(C=CN12)C(=O)N3CCC[C@@H](N)C3)C4=CC5=CC=CC=C5N4CC6=CC=C(F)C=C6
InChI InChI=1S/C29H28FN5O/c1-19-28(32-27-16-22(12-14-34(19)27)29(36)33-13-4-6-24(31)18-33)26-15-21-5-2-3-7-25(21)35(26)17-20-8-10-23(30)11-9-20/h2-3,5,7-12,14-16,24H,4,6,13,17-18,31H2,1H3/t24-/m1/s1
InChI Key DUVCPNSLXBKGOK-XMMPIXPASA-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
JBI-589 inhibits NET formation in vitro, and provides efficacy in mouse arthritis models in vivo [2]. It has also been reported to inhibit progression of primary tumours and metastases in mouse xenograft models [1].
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 4 Hs Inhibitor Inhibition 6.0 – 7.0 pIC50 - 2-3
⤷ pIC50 6.9 (IC50 1.22x10-7 M) [2]
Description: Inhibition of PADI4 enzymatic activity in vitro, in a biochemical assay measuring ammonia release
pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [3]
Description: Measuring inhibition of histone citrullination in neutrophils