PBT-3   Click here for help

GtoPdb Ligand ID: 9755

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: PBT-3 is a stable hepoxilin analogue, that antagonises hepoxilin effects in vitro and in vivo [3-4]. Hepoxilin A3 is an unstable lipid mediator (a proinflammatory eicosanoid derived from arachadonic acid) that acts as a potent neutrophil chemoattractant in the acute phase of the inflammatory response, and has been implicated in the process of NETosis by human neutrophils [1].
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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 3
Hydrogen bond donors 1
Rotatable bonds 18
Topological polar surface area 46.53
Molecular weight 416.33
XLogP 9.27
No. Lipinski's rules broken 2

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 CCCCCC=CCC(C(C1CC1)C(C=CCC=CCCCC(=O)OC)O)C1CC1
Isomeric SMILES CCCCC/C=C\CC(C(C1CC1)[C@H](/C=C\C/C=C\CCCC(=O)OC)O)C1CC1
InChI InChI=1S/C27H44O3/c1-3-4-5-6-9-12-15-24(22-18-19-22)27(23-20-21-23)25(28)16-13-10-7-8-11-14-17-26(29)30-2/h7-9,12-13,16,22-25,27-28H,3-6,10-11,14-15,17-21H2,1-2H3/b8-7-,12-9-,16-13-/t24?,25-,27?/m0/s1
InChI Key ODNVBPFEZJHAAU-OBNWJGEWSA-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. Douda DN, Grasemann H, Pace-Asciak C, Palaniyar N. (2015)
A lipid mediator hepoxilin A3 is a natural inducer of neutrophil extracellular traps in human neutrophils.
Mediators Inflamm, 2015: 520871. [PMID:25784781]
2. Pace-Asciak CR. (2015)
Pathophysiology of the hepoxilins.
Biochim Biophys Acta, 1851 (4): 383-96. [PMID:25240838]
3. Qiao N, Reynaud D, Demin P, Halushka PV, Pace-Asciak CR. (2003)
The thromboxane receptor antagonist PBT-3, a hepoxilin stable analog, selectively antagonizes the TPalpha isoform in transfected COS-7 cells.
J Pharmacol Exp Ther, 307 (3): 1142-7. [PMID:14560042]
4. Reynaud D, Hinek A, Pace-Asciak CR. (2002)
The hepoxilin analog PBT-3 inhibits heparin-activated platelet aggregation evoked by ADP.
FEBS Lett, 515 (1-3): 58-60. [PMID:11943194]
5. Siangjong L, Goldman DH, Kriska T, Gauthier KM, Smyth EM, Puli N, Kumar G, Falck JR, Campbell WB. (2017)
Vascular hepoxilin and trioxilins mediate vasorelaxation through TP receptor inhibition in mouse arteries.
Acta Physiol (Oxf), 219 (1): 188-201. [PMID:26666460]