xanomeline   Click here for help

GtoPdb Ligand ID: 57

Synonyms: Cobenfy® | KarXT | LY 246708
Approved drug PDB Ligand
xanomeline is an approved drug (FDA (2024))
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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2D Structure
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Physico-chemical Properties
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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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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
Bioactivity Comments
Xanomeline selectively targets M1 and M4 receptors in the brain without modulating dopamine D2 receptor activity.
Selectivity at GPCRs
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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