compound 23 [PMID: 35767390]   Click here for help

GtoPdb Ligand ID: 12046

Synonyms: IL-17 modulator 4
PDB Ligand
Compound class: Synthetic organic
Comment: This is a small synthetic molecule that has been demonstrated to disrupt the interaction between the two monomer peptides of the functional interleukin 17A (IL-17A) homodimer (IL-17AA) [1]. Compound 23 was designed as an orally bioavailable agent, for potential to disrupt IL-17A signalling via the IL-17 receptor (principally the IL-17RA/IL-17RC heterodimer), to induce an anti-inflammatory effect in diseases like psoriasis, which are driven by abnormally high IL-17AA expression levels. The 3D structure of compound 23 in complex with the human IL-17AA dimer has been resolved by X-ray crystallography (PDB ID 7AMA). The chemical and physical properties of compound 23 satisfy Lipinski's rule of five for druglikeness [2].
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 6
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 104.7
Molecular weight 474.27
XLogP 5.34
No. Lipinski's rules broken 1
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 O=C([C@H](C(C1CC1)C1CC1)NC(=O)c1ccnn1C(C)C)Nc1ccc(cc1)c1c(C)n[nH]c1C
Isomeric SMILES n1(nccc1C(=O)N[C@@H](C(C1CC1)C1CC1)C(=O)Nc1ccc(cc1)c1c([nH]nc1C)C)C(C)C
InChI InChI=1S/C27H34N6O2/c1-15(2)33-22(13-14-28-33)26(34)30-25(24(19-5-6-19)20-7-8-20)27(35)29-21-11-9-18(10-12-21)23-16(3)31-32-17(23)4/h9-15,19-20,24-25H,5-8H2,1-4H3,(H,29,35)(H,30,34)(H,31,32)/t25-/m0/s1
InChI Key CQKVACARDGYEMU-VWLOTQADSA-N
Bioactivity Comments
Compound 23 inhibits IL-8 release by HEKa cells that have been costimulated with glycosylated IL-17A and TNFα, with an EC50 of 14 nM.
Selectivity at ligand targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
IL-17A Hs Inhibitor Binding 7.5 pKd - 1
⤷ pKd 7.5 (Kd 3.2x10-8 M) [1]
Description: Binding affinity of 23 for hIL-17A in a SPR assay