xanomeline   Click here for help

GtoPdb Ligand ID: 57

Synonyms: LY 246708
PDB Ligand
Compound class: Synthetic organic
Comment: Xanomeline is a muscarinic receptor agonist, with preference for the M1 and M4 receptor subtypes [2,8,12]. It also has antagonist activity at 5-HT2 receptors, and agonist activity at 5-HT1 receptors [10]. Xanomeline was investigated for potential to improve cognition in Alzheimer's disease (AD) patients, but activation of muscarinic receptors in the gastrointestinal tract caused severe nausea and diarrhoea, and this adverse effect led to discontinuation of xanomeline's clinical development for AD.
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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 CDK toolkit. 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 0
Rotatable bonds 7
Topological polar surface area 66.49
Molecular weight 281.16
XLogP 3.34
No. Lipinski's rules broken 0
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.

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Canonical SMILES CCCCCCOc1nsnc1C1=CCCN(C1)C
Isomeric SMILES CCCCCCOc1nsnc1C1=CCCN(C1)C
InChI InChI=1S/C14H23N3OS/c1-3-4-5-6-10-18-14-13(15-19-16-14)12-8-7-9-17(2)11-12/h8H,3-7,9-11H2,1-2H3
InChI Key JOLJIIDDOBNFHW-UHFFFAOYSA-N
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
5-HT1D receptor Hs Agonist Full agonist 8.2 pKi - 10
⤷ pKi 8.2 [10]
5-HT2B receptor Hs Antagonist Antagonist 7.7 pKi - 10
⤷ pKi 7.7 [10]
M4 receptor Hs Agonist Partial agonist 7.4 – 7.7 pKi - 8-10,12
⤷ pKi 7.4 – 7.7 [8-10,12]
5-HT2C receptor Hs Antagonist Antagonist 7.4 pKi - 10
⤷ pKi 7.4 [10]
5-HT1B receptor Hs Agonist Full agonist 7.3 pKi - 10
⤷ pKi 7.3 [10]
M1 receptor Hs Agonist Partial agonist 6.7 – 7.9 pKi - 2,9-10,12
⤷ pKi 6.7 – 7.9 [2,9-10,12]
M3 receptor Hs Agonist Partial agonist 7.2 – 7.4 pKi - 9-10,12
⤷ pKi 7.2 – 7.4 [9-10,12]
5-HT1A receptor Hs Agonist Full agonist 7.2 pKi - 10
⤷ pKi 7.2 [10]
M2 receptor Hs Agonist Full agonist 6.9 – 7.4 pKi - 9-10,12
⤷ pKi 6.9 – 7.4 [9-10,12]
M5 receptor Hs Agonist Partial agonist 6.7 – 7.4 pKi - 6,9-10,12
⤷ pKi 6.7 – 7.4 [6,9-10,12]
5-HT2A receptor Hs Antagonist Antagonist 6.9 pKi - 10
⤷ pKi 6.9 [10]
5-HT7 receptor Hs Agonist Full agonist 6.9 pKi - 10
⤷ pKi 6.9 [10]
5-HT1F receptor Hs Agonist Full agonist 6.5 pKi - 10
⤷ pKi 6.5 [10]
5-HT6 receptor Hs Agonist Full agonist 5.9 pKi - 10
⤷ pKi 5.9 [10]
5-ht1e receptor Hs Agonist Full agonist 5.6 pKi - 10
⤷ pKi 5.6 [10]
Ligand mentioned in the following text fields
Acetylcholine receptors (muscarinic) comments