conessine   Click here for help

GtoPdb Ligand ID: 8981

Compound class: Natural product
Comment: Conessine is an alkaloid obtained from the bark and seeds of Holarrhena antidysenterica trees. It binds with high affinity to rat and human histamine H3 receptors in radio-ligand binding assays, acting as a receptor antagonist [2-3]. H3 antagonists are being researched as potential drugs for the treatment of neurodegenerative conditions and for their stimulant and nootropic effects. For example, pitolisant is in clinical trial for Parkinson's disease, narcolepsy, cataplexy and excessive daytime sleepiness.
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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 2
Hydrogen bond donors 0
Rotatable bonds 1
Topological polar surface area 6.48
Molecular weight 356.32
XLogP 5
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 CN(C1CCC2(C(=CCC3C2CCC24C3CCC4C(N(C2)C)C)C1)C)C
Isomeric SMILES CN([C@H]1CC[C@]2(C(=CC[C@@H]3[C@@H]2CC[C@]24[C@H]3CC[C@@H]4[C@@H](N(C2)C)C)C1)C)C
InChI InChI=1S/C24H40N2/c1-16-20-8-9-22-19-7-6-17-14-18(25(3)4)10-12-23(17,2)21(19)11-13-24(20,22)15-26(16)5/h6,16,18-22H,7-15H2,1-5H3/t16-,18-,19+,20+,21-,22-,23-,24-/m0/s1
InChI Key GPLGAQQQNWMVMM-MYAJQUOBSA-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. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015)
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.
Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]
2. Santora VJ, Covel JA, Hayashi R, Hofilena BJ, Ibarra JB, Pulley MD, Weinhouse MI, Sengupta D, Duffield JJ, Semple G et al.. (2008)
A new family of H3 receptor antagonists based on the natural product Conessine.
Bioorg Med Chem Lett, 18 (4): 1490-4. [PMID:18194865]
3. Zhao C, Sun M, Bennani YL, Gopalakrishnan SM, Witte DG, Miller TR, Krueger KM, Browman KE, Thiffault C, Wetter J et al.. (2008)
The alkaloid conessine and analogues as potent histamine H3 receptor antagonists.
J Med Chem, 51 (17): 5423-30. [PMID:18683917]