WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526719
CAS#: 1265917-14-3 (HCl)
Description: E-52862, also known as S1RA and MR390, is a selective sigma-1 receptor antagonist, with a reported binding affinity of Ki = 17.0 ± 7.0 nM, selective over the sigma-2 receptor and against a panel of other 170 receptors, enzymes, transporters and ion channels. In preclinical studies, S1RA has demonstrated efficacy in relieving neuropathic pain and pain in other sensitizing conditions, associated with an improvement of the emotional negative state. E-52862 attenuates neuropathic pain of different aetiology in rats.
Hodoodo Cat#: H526719
Name: E-52862 HCl
CAS#: 1265917-14-3 (HCl)
Chemical Formula: C20H24ClN3O2
Exact Mass: 0.00
Molecular Weight: 373.880
Elemental Analysis: C, 64.25; H, 6.47; Cl, 9.48; N, 11.24; O, 8.56
Related CAS #: 1265917-14-3 (HCl) 878141-96-9 (free base)
Synonym: E-52862; E 52862; E52862; S1RA; E-52862 HCl; E-52862 hydrochloride; S1RA hydrochloride; MR390; MR 390; MR-390;
IUPAC/Chemical Name: 4-(2-((5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yl)oxy)ethyl)morpholine hydrochloride
InChi Key: SHRYQZBTQDMGLZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H23N3O2.ClH/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;1H
SMILES Code: CC1=CC(OCCN2CCOCC2)=NN1C3=CC=C4C=CC=CC4=C3.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | S1RA hydrochloride (E-52862 hydrochloride) is a potent and selective sigma-1 receptor(σ1R, Ki=17 nM) antagonist. |
| In vitro activity: | The functional activity of compound 28 (E-52862) was evaluated using phenytoin, a low potency allosteric modulator of σ1R that shifts known σ1R agonists to significantly higher affinities (Ki ratios without phenytoin vs with phenytoin of >1), while σ1R antagonists show small or no shift to lower affinity values (Ki ratios without phenytoin vs with phenytoin of ≤1). Compound 28 was shown to be a σ1R antagonist on account of a small shift to lower affinity being observed when incubated in the presence of phenytoin (Ki(without phenytoin)/Ki(with phenytoin) = 0.8). Reference: J Med Chem. 2012 Oct 11;55(19):8211-24. https://pubmed.ncbi.nlm.nih.gov/22784008/ |
| In vivo activity: | The volumetric analysis of the in vivo MRI data showed that neither surgery nor intracerebroventricular (icv) administration significantly changed the total brain volume (437.9 ± 31.1 and. 456.7 ± 24.8, respectively; sham-operated mice 441.4 ± 26.3 mm3). However, pMCAO produced severe injury in mice when examined 48 h after ischaemia (Fig. 1a). Injury was mostly apparent in the cerebral cortex, and the infarct volume was estimated as affecting 9.7 ± 1.8% of the total brain volume. No damage was observed in the sham-operated mice. Compared with untreated mice, the administration of S1RA 1 h post-surgery improved stroke outcomes (an approximate 50% reduction in the infarct size to 3.48 ± 0.9% of the total brain volume) after permanent cerebral ischaemia (Fig. 1a). Reference: Mol Neurobiol. 2018; 55(6): 4940–4951. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948242/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.5 | 135.07 | |
| DMF | 10.0 | 26.75 | |
| DMF:PBS (pH 7.2) (1:5) | 0.2 | 0.43 | |
| Water | 16.7 | 44.59 |
The following data is based on the product molecular weight 373.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Díaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C, Serafini MT, Burgueño J, Zamanillo D, Merlos M, Vela JM, Almansa C. 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. 2012 Oct 11;55(19):8211-24. doi: 10.1021/jm3007323. Epub 2012 Jul 27. PMID: 22784008. 2. Sánchez-Blázquez P, Pozo-Rodrigálvarez A, Merlos M, Garzón J. The Sigma-1 Receptor Antagonist, S1RA, Reduces Stroke Damage, Ameliorates Post-Stroke Neurological Deficits and Suppresses the Overexpression of MMP-9. Mol Neurobiol. 2018 Jun;55(6):4940-4951. doi: 10.1007/s12035-017-0697-x. Epub 2017 Aug 5. PMID: 28779350; PMCID: PMC5948242. 3. Gris G, Portillo-Salido E, Aubel B, Darbaky Y, Deseure K, Vela JM, Merlos M, Zamanillo D. The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats. Sci Rep. 2016 Apr 18;6:24591. doi: 10.1038/srep24591. PMID: 27087602; PMCID: PMC4834548. |
| In vitro protocol: | 1. Díaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C, Serafini MT, Burgueño J, Zamanillo D, Merlos M, Vela JM, Almansa C. 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. 2012 Oct 11;55(19):8211-24. doi: 10.1021/jm3007323. Epub 2012 Jul 27. PMID: 22784008. |
| In vivo protocol: | 1. Sánchez-Blázquez P, Pozo-Rodrigálvarez A, Merlos M, Garzón J. The Sigma-1 Receptor Antagonist, S1RA, Reduces Stroke Damage, Ameliorates Post-Stroke Neurological Deficits and Suppresses the Overexpression of MMP-9. Mol Neurobiol. 2018 Jun;55(6):4940-4951. doi: 10.1007/s12035-017-0697-x. Epub 2017 Aug 5. PMID: 28779350; PMCID: PMC5948242. 2. Gris G, Portillo-Salido E, Aubel B, Darbaky Y, Deseure K, Vela JM, Merlos M, Zamanillo D. The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats. Sci Rep. 2016 Apr 18;6:24591. doi: 10.1038/srep24591. PMID: 27087602; PMCID: PMC4834548. |
1: Paniagua N, Girón R, Goicoechea C, López-Miranda V, Vela JM, Merlos M, Martín Fontelles MI. Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats. Eur J Pain. 2016 Jun 24. doi: 10.1002/ejp.897. [Epub ahead of print] PubMed PMID: 27341510.
2: Gris G, Portillo-Salido E, Aubel B, Darbaky Y, Deseure K, Vela JM, Merlos M, Zamanillo D. The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats. Sci Rep. 2016 Apr 18;6:24591. doi: 10.1038/srep24591. PubMed PMID: 27087602; PubMed Central PMCID: PMC4834548.
3: Romero L, Merlos M, Vela JM. Antinociception by Sigma-1 Receptor Antagonists: Central and Peripheral Effects. Adv Pharmacol. 2016;75:179-215. doi: 10.1016/bs.apha.2015.11.003. Epub 2016 Jan 27. PubMed PMID: 26920013.
4: Täubel J, Ferber G, Lorch U, Wang D, Sust M, Camm AJ. 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. 2015 Aug 20;10(8):e0136369. doi: 10.1371/journal.pone.0136369. eCollection 2015. PubMed PMID: 26291080; PubMed Central PMCID: PMC4546378.
5: Vela JM, Merlos M, Almansa C. Investigational sigma-1 receptor antagonists for the treatment of pain. Expert Opin Investig Drugs. 2015;24(7):883-96. doi: 10.1517/13543784.2015.1048334. Epub 2015 Jun 3. Review. PubMed PMID: 26037209.
6: Ferber G, Wang D, Täubel J. Concentration-effect modeling based on change from baseline to assess the prolonging effect of drugs on QTc together with an estimate of the circadian time course. J Clin Pharmacol. 2014 Dec;54(12):1400-6. doi: 10.1002/jcph.347. Epub 2014 Jun 27. PubMed PMID: 24935561.
7: Gris G, Merlos M, Vela JM, Zamanillo D, Portillo-Salido E. S1RA, a selective sigma-1 receptor antagonist, inhibits inflammatory pain in the carrageenan and complete Freund's adjuvant models in mice. Behav Pharmacol. 2014 Jun;25(3):226-35. doi: 10.1097/FBP.0000000000000038. PubMed PMID: 24776490.
8: Vidal-Torres A, Fernández-Pastor B, Carceller A, Vela JM, Merlos M, Zamanillo D. Effects of the selective sigma-1 receptor antagonist S1RA on formalin-induced pain behavior and neurotransmitter release in the spinal cord in rats. J Neurochem. 2014 May;129(3):484-94. doi: 10.1111/jnc.12648. Epub 2014 Jan 29. PubMed PMID: 24384038.
9: 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, Entrena JM, Cobos EJ. Modulation of peripheral μ-opioid analgesia by σ1 receptors. J Pharmacol Exp Ther. 2014 Jan;348(1):32-45. doi: 10.1124/jpet.113.208272. Epub 2013 Oct 23. PubMed PMID: 24155346.
10: Vidal-Torres A, de la Puente B, Rocasalbas M, Touriño C, Bura SA, Fernández-Pastor B, Romero L, Codony X, Zamanillo D, Buschmann H, Merlos M, Baeyens JM, Maldonado R, Vela JM. Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects. Eur J Pharmacol. 2013 Jul 5;711(1-3):63-72. doi: 10.1016/j.ejphar.2013.04.018. Epub 2013 Apr 28. PubMed PMID: 23632394.
11: Laurini E, Da Col V, Wünsch B, Pricl S. Analysis of the molecular interactions of the potent analgesic S1RA with the σ1 receptor. Bioorg Med Chem Lett. 2013 May 15;23(10):2868-71. doi: 10.1016/j.bmcl.2013.03.087. Epub 2013 Mar 30. PubMed PMID: 23582276.
12: Collina S, Gaggeri R, Marra A, Bassi A, Negrinotti S, Negri F, Rossi D. Sigma receptor modulators: a patent review. Expert Opin Ther Pat. 2013 May;23(5):597-613. doi: 10.1517/13543776.2013.769522. Epub 2013 Feb 7. Review. PubMed PMID: 23387851.
13: Nieto FR, Cendán CM, Sánchez-Fernández C, Cobos EJ, Entrena JM, Tejada MA, Zamanillo D, Vela JM, Baeyens JM. Role of sigma-1 receptors in paclitaxel-induced neuropathic pain in mice. J Pain. 2012 Nov;13(11):1107-21. doi: 10.1016/j.jpain.2012.08.006. Epub 2012 Oct 12. PubMed PMID: 23063344.
14: Wünsch B. The σ(1) receptor antagonist S1RA is a promising candidate for the treatment of neurogenic pain. J Med Chem. 2012 Oct 11;55(19):8209-10. doi: 10.1021/jm3011993. Epub 2012 Sep 5. PubMed PMID: 22951043.
15: Díaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C, Serafini MT, Burgueño J, Zamanillo D, Merlos M, Vela JM, Almansa C. 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. 2012 Oct 11;55(19):8211-24. doi: 10.1021/jm3007323. Epub 2012 Jul 27. PubMed PMID: 22784008.
16: Abadias M, Escriche M, Vaqué A, Sust M, Encina G. Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies. Br J Clin Pharmacol. 2013 Jan;75(1):103-17. doi: 10.1111/j.1365-2125.2012.04333.x. PubMed PMID: 22607269; PubMed Central PMCID: PMC3555050.
17: Romero L, Zamanillo D, Nadal X, Sánchez-Arroyos R, Rivera-Arconada I, Dordal A, Montero A, Muro A, Bura A, Segalés C, Laloya M, Hernández E, Portillo-Salido E, Escriche M, Codony X, Encina G, Burgueño J, Merlos M, Baeyens JM, Giraldo J, López-García JA, Maldonado R, Plata-Salamán CR, Vela JM. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization. Br J Pharmacol. 2012 Aug;166(8):2289-306. doi: 10.1111/j.1476-5381.2012.01942.x. PubMed PMID: 22404321; PubMed Central PMCID: PMC3448894.
