Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H23N3O2.ClH |
| Molecular Weight | 373.876 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CC1=CC(OCCN2CCOCC2)=NN1C3=CC4=C(C=CC=C4)C=C3
InChI
InChIKey=SHRYQZBTQDMGLZ-UHFFFAOYSA-N
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
| Molecular Formula | C20H23N3O2 |
| Molecular Weight | 337.4155 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27087602 | https://www.ncbi.nlm.nih.gov/pubmed/22607269http://adisinsight.springer.com/drugs/800031669Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22784008 | https://www.ncbi.nlm.nih.gov/pubmed/22404321
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27087602 | https://www.ncbi.nlm.nih.gov/pubmed/22607269http://adisinsight.springer.com/drugs/800031669
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22784008 | https://www.ncbi.nlm.nih.gov/pubmed/22404321
4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862) is an 1-arylpyrazole class of sigma-1 receptor antagonist. Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of sigma-1 receptors in the CNS was significantly correlated with the antinociceptive effects. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of sigma-1 receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. Esteve is developing E 52862 for the treatment of several pain indications, including diabetic neuropathies, chemotherapy-induced neuropathic pain, postherpetic neuralgia, postoperative pain. Phase II development of this first-in-class agent is underway in Romania, Spain and Greece.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Q99720|||Q7Z653 Gene ID: 10280.0 Gene Symbol: SIGMAR1 Target Organism: Homo sapiens (Human) |
17.0 nM [Ki] | ||
Target ID: CHEMBL287 |
17.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5580.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26291080 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-52862 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
155911 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26291080 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-52862 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
41.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26291080 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-52862 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
400 mg 1 times / day multiple, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
healthy |
|
800 mg single, oral Highest studied dose |
healthy |
Other AEs: headache, Dizziness... Other AEs: headache (19.4%) Sources: Dizziness (19.4%) Abnormal thinking (9.7%) Dissociation (6.5%) Euphoric mood (6.5%) Euphoric mood (3.2%) Nausea (12.9%) Palpitations (3.2%) Sinus tachycardia (6.5%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Nausea | 12.9% | 800 mg single, oral Highest studied dose |
healthy |
| Dizziness | 19.4% | 800 mg single, oral Highest studied dose |
healthy |
| headache | 19.4% | 800 mg single, oral Highest studied dose |
healthy |
| Euphoric mood | 3.2% | 800 mg single, oral Highest studied dose |
healthy |
| Palpitations | 3.2% | 800 mg single, oral Highest studied dose |
healthy |
| Dissociation | 6.5% | 800 mg single, oral Highest studied dose |
healthy |
| Euphoric mood | 6.5% | 800 mg single, oral Highest studied dose |
healthy |
| Sinus tachycardia | 6.5% | 800 mg single, oral Highest studied dose |
healthy |
| Abnormal thinking | 9.7% | 800 mg single, oral Highest studied dose |
healthy |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats. | 2016-04-18 |
|
| Effects of the selective sigma-1 receptor antagonist S1RA on formalin-induced pain behavior and neurotransmitter release in the spinal cord in rats. | 2014-05 |
|
| Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies. | 2013-01 |
|
| 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). | 2012-10-11 |
|
| Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization. | 2012-08 |
Patents
Sample Use Guides
Three randomized, double-blind, placebo-controlled trials evaluated single oral doses (5-500 mg, study 101; 500-800 mg, study 106) and multiple doses (50-400 mg once daily for 8 days, study 102) of S1RA (API-001)
Route of Administration:
Oral
E-52862 (API-001) is a selective sigma-1 receptor (σ1R) antagonist, with 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. Binding affinity was performed to human σ1R transfected HEK-293 membranes using [3H](+)-pentazocine as radioligand.
| Substance Class |
Chemical
Created
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