S1RA hydrochloride

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.

Product information

CAS Number: 1265917-14-3

Molecular Weight: 373.88

Formula: C20H24ClN3O2

Chemical Name: 4-(2-((5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yl)oxy)ethyl)morpholine hydrochloride

Smiles: Cl.CC1=CC(=NN1C1=CC2=CC=CC=C2C=C1)OCCN1CCOCC1

InChiKey: SHRYQZBTQDMGLZ-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: ≥ 57 mg/mL

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

S1RA behaved as a highly selective σ1 receptor antagonist. It showed high affinity for human (Ki= 17 nM) and guinea pig (Ki= 23.5 nM) σ1 receptors but no significant affinity for the σ2 receptors (Ki > 1000 nM for guinea pig and rat σ2 receptors). Moderate affinity (Ki= 328 nM) and antagonistic activity, with very low potency (IC50= 4700 nM) was found at the human 5-HT2B receptor. S1RA showed no significant affinity (Ki > 1 μM or % inhibition at 1 μM < 50%) for other additional 170 targets (receptors, transporters, ion channels and enzymes).

In Vivo:

Control (non-operated) and nerve-injured mice received a single or repeated (twice daily for 12 days) i.p. administration of S1RA at 25 mg·kg?1, the same dose used for the assessment of behavioural hypersensitivity in the chronic treatment study. Acute treatment was given on day 12 post-surgery and repeated treatment with S1RA started the day of surgery, as in the behavioural studies. Intrathecal pre-treatment with idazoxan prevented the systemic S1RA antinociceptive effect, suggesting that the S1RA antinociception depends on the activation of spinal α2 -adrenoceptors which, in turn, could induce an inhibition of formalin-evoked glutamate release. When administered locally, intrathecal S1RA inhibited only the flinching behavior, whereas intracerebroventricularly or intraplantarly injected also attenuated the lifting/licking behavior.

References:

1. Díaz JL, et al. 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.
2. Romero L, et al. 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.
3. Vidal-Torres A, et al. 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 Jan 3.

Products are for research use only. Not for human use.