BTP2   Click here for help

GtoPdb Ligand ID: 2438

Synonyms: YM-58483
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BTP2 (YM-58483) is a small molecule store-operated Ca2+ release-activated Ca2+ (CRAC) channel inhibitor [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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View interactive charts of activity data across species

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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 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 5
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 100.42
Molecular weight 421.04
XLogP 3.51
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 O=C(c1snnc1C)Nc1ccc(cc1)n1nc(cc1C(F)(F)F)C(F)(F)F
Isomeric SMILES O=C(c1snnc1C)Nc1ccc(cc1)n1nc(cc1C(F)(F)F)C(F)(F)F
InChI InChI=1S/C15H9F6N5OS/c1-7-12(28-25-23-7)13(27)22-8-2-4-9(5-3-8)26-11(15(19,20)21)6-10(24-26)14(16,17)18/h2-6H,1H3,(H,22,27)
InChI Key XPRZIORDEVHURQ-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/)
Immunopharmacology Comments
CRAC channels form a network essential for activation of the adaptive immune response. They are expressed mainly bt non-excitable cells including T-lymphocytes and mast cells. Activation of CRAC channels in the plasma membranes of these cells results in alteration in NFAT-dependent expression of several cytokines including interleukin-2. Inhibition of calcium influx by altering CRAC channel activity has potential as an effective strategy for the treatment of autoimmune and inflammatory diseases, whilst minimising the adverse effects (nephrotoxicity and neurotoxicity) commonly produced by calcineurin inhibitors used as immunosuppressive agents.

CRAC channels have been implicated in the pathogenesis of rheumatoid arthritis (RA), and inhibitors investigated as clinical candidates for this disease, and others [4]. BTP2 (YM-58483) is a CRAC channel inhibitor. However, despite showing some anti-inflammatory activity in RA models, YM-58483 was associated with safety issues including hepatic and renal toxicity, and hyperglycemia in mice [2].