compound 8a [PMID: 23713581]   Click here for help

GtoPdb Ligand ID: 8856

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 8a was designed as a small-molecule inhibitor of the lymphoid-specific non-receptor tyrosine phosphatase, LYP (PTPN22) [1]. PTPN22 directly dephosphorylates several kinase enzymes, effecting negative regulation of T-cell receptor (TCR) signaling [3], and is implicated in autoimmune diseases [4].
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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
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 4
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 109
Molecular weight 503.11
XLogP 6.66
No. Lipinski's rules broken 1

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 CCCNC(=O)COc1ccc(cc1)c1oc2c(c1C#Cc1cccc(c1)Cl)cc(c(c2)O)C(=O)O
Isomeric SMILES CCCNC(=O)COc1ccc(cc1)c1oc2c(c1C#Cc1cccc(c1)Cl)cc(c(c2)O)C(=O)O
InChI InChI=1S/C28H22ClNO6/c1-2-12-30-26(32)16-35-20-9-7-18(8-10-20)27-21(11-6-17-4-3-5-19(29)13-17)22-14-23(28(33)34)24(31)15-25(22)36-27/h3-5,7-10,13-15,31H,2,12,16H2,1H3,(H,30,32)(H,33,34)
InChI Key ZAKVHDWXAFAMTH-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/)
References
1. He Y, Liu S, Menon A, Stanford S, Oppong E, Gunawan AM, Wu L, Wu DJ, Barrios AM, Bottini N et al.. (2013)
A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases.
J Med Chem, 56 (12): 4990-5008. [PMID:23713581]
2. Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, Nika K, Tautz L, Taskén K, Cucca F et al.. (2005)
Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.
Nat Genet, 37 (12): 1317-9. [PMID:16273109]
3. Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR et al.. (2006)
Identification of substrates of human protein-tyrosine phosphatase PTPN22.
J Biol Chem, 281 (16): 11002-10. [PMID:16461343]
4. Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. (2007)
Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases.
Proc Natl Acad Sci USA, 104 (50): 19767-72. [PMID:18056643]