compound 19a [PMID: 26506089]   Click here for help

GtoPdb Ligand ID: 9842

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 19a is the most potent of a series of STAT6 inhibitors reported by Mandal et al. (2015) [1]. STAT6 inhibitors are being developed for their potential to inhibit the expression of genes contributing to asthma. Compound 19a is a phosphopeptide mimic that blocks interaction of the IL-4 and IL-13 receptors with the SH2 domain of STAT6, thereby preventing the downstream transcriptional sequelae of STAT6 activation. The structure is claimed in patent WO2014182928 [2].
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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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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 9
Hydrogen bond donors 3
Rotatable bonds 13
Topological polar surface area 146.29
Molecular weight 745.14
XLogP 5.27
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 Ic1ccc(cc1)N(C(=O)C1CCCN1C(=O)C(C(C)(C)C)NC(=O)C=C(c1ccc(cc1)OP(=O)(O)O)C)c1ccccc1
Isomeric SMILES Ic1ccc(cc1)N(C(=O)[C@@H]1CCCN1C(=O)[C@H](C(C)(C)C)NC(=O)/C=C(/c1ccc(cc1)OP(=O)(O)O)\C)c1ccccc1
InChI InChI=1S/C33H37IN3O7P/c1-22(23-12-18-27(19-13-23)44-45(41,42)43)21-29(38)35-30(33(2,3)4)32(40)36-20-8-11-28(36)31(39)37(25-9-6-5-7-10-25)26-16-14-24(34)15-17-26/h5-7,9-10,12-19,21,28,30H,8,11,20H2,1-4H3,(H,35,38)(H2,41,42,43)/b22-21+/t28-,30+/m0/s1
InChI Key CGLGRSOJPUXNFA-YVXBOAIISA-N
No information available.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Elevated levels of IL-4 and IL-13 in the airways of asthmatic patients contribute to mucus production, airway hyperresponsiveness, eosinophil recruitment and T-helper cell 2 (Th2) activation which results in immunoglobulin class switching to IgE, and inflammation. These cytokines function through a common receptor alpha subunit, that is phosphorylated on tyrosine residues by JAK1, JAK3, or Tyk2 upon ligand engagement. STAT6 is then recruited to the receptor pTyr residues via its SH2 domain, dimerises and translocates to the nucleus where it modulates the the expression of genes that further promote asthma and airway hyperresponsiveness. Prevention of STAT6 activation using drug-like molecules is a strategy being evaluated for anti-asthmatic potential.