E-52862   Click here for help

GtoPdb Ligand ID: 10431

Synonyms: compound 28 [PMID: 22784008] | E52862 | MR309 [4] | sigma 1 receptor antagonist (S1RA) [10]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: E-52862 is a σ1 receptor antagonist [6]. It has been shown to exert dose-dependent antinociceptive effects in several neuropathic pain models.
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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 0
Rotatable bonds 5
Topological polar surface area 39
Molecular weight 337.18
XLogP 3.36
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 Cc1cc(nn1c1ccc2c(c1)cccc2)OCCN1CCOCC1
Isomeric SMILES Cc1cc(nn1c1ccc2c(c1)cccc2)OCCN1CCOCC1
InChI InChI=1S/C20H23N3O2/c1-16-14-20(25-13-10-22-8-11-24-12-9-22)21-23(16)19-7-6-17-4-2-3-5-18(17)15-19/h2-7,14-15H,8-13H2,1H3
InChI Key DGPGXHRHNRYVDH-UHFFFAOYSA-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. Bruna J, Velasco R. (2018)
Sigma-1 receptor: a new player in neuroprotection against chemotherapy-induced peripheral neuropathy.
Neural Regen Res, 13 (5): 775-778. [PMID:29862996]
2. Bruna J, Videla S, Argyriou AA, Velasco R, Villoria J, Santos C, Nadal C, Cavaletti G, Alberti P, Briani C et al.. (2018)
Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial.
Neurotherapeutics, 15 (1): 178-189. [PMID:28924870]
3. Carcolé M, Zamanillo D, Merlos M, Fernández-Pastor B, Cabañero D, Maldonado R. (2019)
Blockade of the Sigma-1 Receptor Relieves Cognitive and Emotional Impairments Associated to Chronic Osteoarthritis Pain.
Front Pharmacol, 10: 468. [PMID:31130863]
4. Castany S, Codony X, Zamanillo D, Merlos M, Verdú E, Boadas-Vaello P. (2019)
Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice.
Front Pharmacol, 10: 222. [PMID:30967775]
5. Dorsey SG. (2018)
Selective Blockade of the Sigma 1 Receptor Has Beneficial Effects on Both Acute and Chronic Oxaliplatin-Induced Peripheral Neuropathy.
Neurotherapeutics, 15 (1): 176-177. [PMID:29110212]
6. Díaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C et al.. (2012)
Synthesis and biological evaluation of the 1-arylpyrazole class of σ(1) receptor antagonists: identification of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862).
J Med Chem, 55 (19): 8211-24. [PMID:22784008]
7. Gris G, Merlos M, Vela JM, Zamanillo D, Portillo-Salido E. (2014)
S1RA, a selective sigma-1 receptor antagonist, inhibits inflammatory pain in the carrageenan and complete Freund's adjuvant models in mice.
Behav Pharmacol, 25 (3): 226-35. [PMID:24776490]
8. Merlos M, Burgueño J, Portillo-Salido E, Plata-Salamán CR, Vela JM. (2017)
Pharmacological Modulation of the Sigma 1 Receptor and the Treatment of Pain.
Adv Exp Med Biol, 964: 85-107. [PMID:28315267]
9. Nieto FR, Cendán CM, Sánchez-Fernández C, Cobos EJ, Entrena JM, Tejada MA, Zamanillo D, Vela JM, Baeyens JM. (2012)
Role of sigma-1 receptors in paclitaxel-induced neuropathic pain in mice.
J Pain, 13 (11): 1107-21. [PMID:23063344]
10. Romero L, Zamanillo D, Nadal X, Sánchez-Arroyos R, Rivera-Arconada I, Dordal A, Montero A, Muro A, Bura A, Segalés C et al.. (2012)
Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.
Br J Pharmacol, 166 (8): 2289-306. [PMID:22404321]
11. Sánchez-Fernández C, Montilla-García Á, González-Cano R, Nieto FR, Romero L, Artacho-Cordón A, Montes R, Fernández-Pastor B, Merlos M, Baeyens JM et al.. (2014)
Modulation of peripheral μ-opioid analgesia by σ1 receptors.
J Pharmacol Exp Ther, 348 (1): 32-45. [PMID:24155346]
12. Tejada MA, Montilla-García A, Cronin SJ, Cikes D, Sánchez-Fernández C, González-Cano R, Ruiz-Cantero MC, Penninger JM, Vela JM, Baeyens JM et al.. (2017)
Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice.
Proc Natl Acad Sci USA, 114 (31): 8396-8401. [PMID:28716934]
13. Täubel J, Ferber G, Lorch U, Wang D, Sust M, Camm AJ. (2015)
Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval--A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity.
PLoS ONE, 10 (8): e0136369. [PMID:26291080]
14. Vidal-Torres A, de la Puente B, Rocasalbas M, Touriño C, Bura SA, Fernández-Pastor B, Romero L, Codony X, Zamanillo D, Buschmann H et al.. (2013)
Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects.
Eur J Pharmacol, 711 (1-3): 63-72. [PMID:23632394]
15. Vidal-Torres A, Fernández-Pastor B, Carceller A, Vela JM, Merlos M, Zamanillo D. (2019)
Supraspinal and Peripheral, but Not Intrathecal, σ1R Blockade by S1RA Enhances Morphine Antinociception.
Front Pharmacol, 10: 422. [PMID:31068818]
16. Wünsch B. (2012)
The σ(1) receptor antagonist S1RA is a promising candidate for the treatment of neurogenic pain.
J Med Chem, 55 (19): 8209-10. [PMID:22951043]