blarcamesine   Click here for help

GtoPdb Ligand ID: 11586

Synonyms: AE-37 | AE37 | Anavex 2-73 | Anavex2-73 | THD-DP-FM
Compound class: Synthetic organic
Comment: Blarcamesine (Anavex2-73) is a Sigma-1 (σ1) protein agonist and muscarinic acetylcholine receptor modulator [6]. Anavex are investigating it for potential to slow progression in neurodegenerative conditions including Parkinson's and Alzheimer's diseases, and Rett syndrome [2]. Anticonvulsant, anti-amnesic, neuroprotective and antidepressant activities in response to blarcamesine have been identified in a number of animal models of neurodegenerative and neurodevelopmental conditions [3-6].
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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 2
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 12.47
Molecular weight 281.18
XLogP 3.63
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 CN(CC1CCOC1(c1ccccc1)c1ccccc1)C
Isomeric SMILES CN(CC1CCOC1(c1ccccc1)c1ccccc1)C
InChI InChI=1S/C19H23NO/c1-20(2)15-18-13-14-21-19(18,16-9-5-3-6-10-16)17-11-7-4-8-12-17/h3-12,18H,13-15H2,1-2H3
InChI Key BOTHKNZTGGXFEQ-UHFFFAOYSA-N
References
1. Hampel H, Williams C, Etcheto A, Goodsaid F, Parmentier F, Sallantin J, Kaufmann WE, Missling CU, Afshar M. (2020)
A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study.
Alzheimers Dement (N Y), 6 (1): e12013. [PMID:32318621]
2. Kaufmann WE, Sprouse J, Rebowe N, Hanania T, Klamer D, Missling CU. (2019)
ANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome.
Pharmacol Biochem Behav, 187: 172796. [PMID:31704481]
3. Lahmy V, Long R, Morin D, Villard V, Maurice T. (2014)
Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model.
Front Cell Neurosci, 8: 463. [PMID:25653589]
4. Lahmy V, Meunier J, Malmström S, Naert G, Givalois L, Kim SH, Villard V, Vamvakides A, Maurice T. (2013)
Blockade of Tau hyperphosphorylation and Aβ₁₋₄₂ generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ₁ receptor agonist, in a nontransgenic mouse model of Alzheimer's disease.
Neuropsychopharmacology, 38 (9): 1706-23. [PMID:23493042]
5. Maurice T. (2016)
Protection by sigma-1 receptor agonists is synergic with donepezil, but not with memantine, in a mouse model of amyloid-induced memory impairments.
Behav Brain Res, 296: 270-278. [PMID:26386305]
6. Villard V, Espallergues J, Keller E, Vamvakides A, Maurice T. (2011)
Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative.
J Psychopharmacol, 25 (8): 1101-17. [PMID:20829307]