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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2D Structure
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Physico-chemical Properties
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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
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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
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]