E-52862

E-52862, also known as sigma-1 receptor antagonist (S1A, S1RA), as well as MR-309, is a selective sigma-1 receptor antagonist, with a reported binding affinity of K_i = 17.0 ± 7.0 nM, selective over the sigma-2 receptor and against a panel of other 170 receptors, enzymes, transporters and ion channels.^[1][2] 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.^[2][3][4][5]

Other namesS1A; S1RA; MR-309

CAS Number

• 878141-96-9

ChemSpider

• 28641653

UNII

• ZW18DSD1H4

Quick facts Clinical data, Other names ...

E-52862

Clinical data
Other names	S1A; S1RA; MR-309
Identifiers
IUPAC name 4-(2-((5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yl)oxy)ethyl)morpholine
CAS Number	878141-96-9
ChemSpider	28641653
UNII	ZW18DSD1H4
ChEMBL	ChEMBL2170062
CompTox Dashboard (EPA)	DTXSID901022521
Chemical and physical data
Formula	C20H23N3O2
Molar mass	337.423 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=CC(OCCN2CCOCC2)=NN1C1=CC=C2C=CC=CC2=C1
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 Key:DGPGXHRHNRYVDH-UHFFFAOYSA-N

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S1RA is being developed by Esteve for the treatment of neuropathic pain and the potentiation of opioid analgesia and has successfully completed Phase I clinical trials showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration.^[6] Phase II clinical trials are currently underway, making S1RA the first selective sigma-1 receptor antagonist evaluated in humans for these conditions.

As of 2025, Phase II trials on human patients have made progress. In European patients with chronic postsurgical pain and painful diabetic neuropathy, the drug showed clinically significant reduction of baseline and worst pain in patients with non-spinal injuries with chronic postsurgical pain. The painful diabetic neuropathy group had a similar reduction in pain, although due to a particularly strong placebo response, more studies will be needed to detangle the true extent of the effects.^[7]