TRAM-34   Click here for help

GtoPdb Ligand ID: 2336

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: TRAM-34 is a KCa3.1 channel blocker.
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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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Click here for structure editor
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 1
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 17.82
Molecular weight 344.11
XLogP 6.47
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 Clc1ccccc1C(n1cccn1)(c1ccccc1)c1ccccc1
Isomeric SMILES Clc1ccccc1C(n1cccn1)(c1ccccc1)c1ccccc1
InChI InChI=1S/C22H17ClN2/c23-21-15-8-7-14-20(21)22(25-17-9-16-24-25,18-10-3-1-4-11-18)19-12-5-2-6-13-19/h1-17H
InChI Key KBFUQFVFYYBHBT-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
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The Ca²⁺-activated K⁺ channel KCa3.1 as a potential new target for the prevention of allograft vasculopathy.
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The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke.
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Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.
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Treatment with the KCa3.1 inhibitor TRAM-34 during diabetic ketoacidosis reduces inflammatory changes in the brain.
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Blocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes.
PLoS ONE, 8 (10): e76740. [PMID:24146918]
9. Köhler R, Wulff H, Eichler I, Kneifel M, Neumann D, Knorr A, Grgic I, Kämpfe D, Si H, Wibawa J, Real R, Borner K, Brakemeier S, Orzechowski HD, Reusch HP, Paul M, Chandy KG, Hoyer J. (2003)
Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis.
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Ca2+ -activated K+ channel-3.1 blocker TRAM-34 alleviates murine allergic rhinitis.
Int Immunopharmacol, 23 (2): 642-8. [PMID:25466273]
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Upregulation of KCa3.1 K(+) channel in mesenteric lymph node CD4(+) T lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease.
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12. Roach KM, Duffy SM, Coward W, Feghali-Bostwick C, Wulff H, Bradding P. (2013)
The K+ channel KCa3.1 as a novel target for idiopathic pulmonary fibrosis.
PLoS ONE, 8 (12): e85244. [PMID:24392001]
13. Shao Z, Gaurav R, Agrawal DK. (2015)
Intermediate-conductance calcium-activated potassium channel KCa3.1 and chloride channel modulate chemokine ligand (CCL19/CCL21)-induced migration of dendritic cells.
Transl Res, 166 (1): 89-102. [PMID:25583444]
14. Wulff H, Miller MJ, Hansel W, Grissmer S, Cahalan MD, Chandy KG. (2000)
Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant.
Proc Natl Acad Sci USA, 97 (14): 8151-6. [PMID:10884437]
15. Yu ZH, Xu JR, Wang YX, Xu GN, Xu ZP, Yang K, Wu DZ, Cui YY, Chen HZ. (2013)
Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma.
Am J Respir Cell Mol Biol, 48 (6): 685-93. [PMID:23492185]
16. Zhang S, Wang X, Ju C, Zhu L, Du Y, Gao C. (2016)
Blockage of K(Ca)3.1 and Kv1.3 channels of the B lymphocyte decreases the inflammatory monocyte chemotaxis.
Int Immunopharmacol, 31: 266-71. [PMID:26795234]