NSC80734   Click here for help

GtoPdb Ligand ID: 10497

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: NSC80734 is a small molecule protein-protein interaction inhibitor that disrupts human IL-18 binding to the ectromelia virus IL-18 binding protein (IL-18BP) [1]. IL-18BP acts as endogenous antagonist of IL-18 activity. By sequestering circulating IL-18 it modulates the amount of free IL-18 able to activate its receptor and downstream signalling cascade. NSC80734 binds in to the interaction site on IL-18 that engages IL-18BP, and thus it acts as an IL-18BP mimetic.
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 8
Hydrogen bond donors 4
Rotatable bonds 10
Topological polar surface area 139.07
Molecular weight 488.16
XLogP 3.87
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 N#Cc1ccc(cc1)NC(=O)Nc1ccc(cc1)Oc1ccc(cc1)NC(=O)Nc1ccc(cc1)C#N
Isomeric SMILES N#Cc1ccc(cc1)NC(=O)Nc1ccc(cc1)Oc1ccc(cc1)NC(=O)Nc1ccc(cc1)C#N
InChI InChI=1S/C28H20N6O3/c29-17-19-1-5-21(6-2-19)31-27(35)33-23-9-13-25(14-10-23)37-26-15-11-24(12-16-26)34-28(36)32-22-7-3-20(18-30)4-8-22/h1-16H,(H2,31,33,35)(H2,32,34,36)
InChI Key NKTXGJQCHFJKQJ-UHFFFAOYSA-N
Immunopharmacology Comments
In a cell-based bioassay NSC80734 dose-dependently inhibited IL-18-induced IFNγ production (IC50 ~250 nM) [1].
As IL-18 is a powerful driver of autoinflammatory diseases, inhibitors of IL-18 signalling are being developed as novel anti-inflammatory therapeutic options. Synthetic IL-18BP (e.g. tadekinig alfa) and monoclonal antibodies that block IL-18 binding to its receptor (IL-18Rα, e.g. GSK1070806) are being tested in clinical trials. Small molecule inhibitors offer many pharmacokinetic/pharmacodynamic benefits over peptide-based therapeutics, so NSC80734 could pave the way for the design of novel small molecule drugs for the treatment of pathological diseases associated with IL-18 bioactivity.